Experimental and Computational Studies of Ruthenium Complexes Bearing Z-Acceptor Aluminum-Based Phosphine Pincer Ligands.

Reaction of [Ru(C6H4PPh2)2(Ph2PC6H4AlMe(THF))H] with CO results in clean conversion to the Ru-Al heterobimetallic complex [Ru(AlMePhos)(CO)3] (1), where AlMePhos is the novel P-Al(Me)-P pincer ligand (o-Ph2PC6H4)2AlMe. Under photolytic conditions, 1 reacts with H2 to give [Ru(AlMePhos)(CO)2(µ-H)H] (2) that is characterized by multinuclear NMR and IR spectroscopies. DFT calculations indicate that 2 features one terminal and one bridging hydride that are respectively anti and syn to the AlMe group. Calculations also define a mechanism for H2 addition to 1 and predict facile hydride exchange in 2 that is also observed experimentally. Reaction of 1 with B(C6F5)3 results in Me abstraction to form the ion pair [Ru(AlPhos)(CO)3][MeB(C6F5)3] (4) featuring a cationic [(o-Ph2PC6H4)2Al]+ ligand, [AlPhos]+. The Ru-Al distance in 4 (2.5334(16) Å) is significantly shorter than that in 1 (2.6578(6) Å), consistent with an enhanced Lewis acidity of the [AlPhos]+ ligand. This is corroborated by a blue shift in both the observed and computed νCO stretching frequencies upon Me abstraction. Electronic structure analyses (QTAIM and EDA-ETS) comparing 1, 4, and the previously reported [Ru(ZnPhos)(CO)3] analogue (ZnPhos = (o-Ph2PC6H4)2Zn) indicate that the Lewis acidity of these pincer ligands increases along the series ZnPhos < AlMePhos < [AlPhos]+.

Measuring, evaluating and improving the effectiveness of invasive predator control programs: Feral cat baiting as a case study.

Reducing the impacts of invasive predators is a key objective for conservation managers, livestock producers and human health agencies globally. The efficacy of invasive predator control programs, however, is highly variable. To improve control efficacy, managers require a fundamental understanding of the factors that contribute to the success or failure of a control program. Using a predator baiting program as a case study, we measured the efficacy of baiting as a control tool to significantly reduce feral cat (Felis catus) populations. We used camera traps and cat-borne GPS collars to monitor changes in feral cat populations at a baited site and an unbaited site, using a Before-After, Control-Impact (BACI) design. We also identified five key elements required for a successful baiting program (bait encounter rate, availability, attractiveness, palatability and lethality) and simultaneously measured these to identify areas for potential improvement. Baiting was ineffective at reducing feral cat populations; collared cat mortality was only 11% (1/9), with camera traps revealing negligible reductions in the number of cat detection events (9%), naïve occupancy (15%), and no significant change in the relative abundance of feral cats (F1,54 = 0.8641, P = 0.357). Several factors contributed to the poor control efficacy. Bait encounter rates were low, with cats active along tracks (where baits were laid) < 4% of the time. Cats encountered only 14% (7/50) of monitored baits, but none were eaten. Initially, baits appeared attractive to cats; however meat ants and desiccation rapidly decreased bait palatability. Bait availability to cats declined rapidly, with 36% of monitored baits (18/50) removed by non-target species within the first 48 h. The mortality of one collared cat and chemical assays confirmed that, on average, each bait contained sufficient 1080 to kill a large (>5 kg) feral cat. Our findings suggest that altering bait deployment patterns, increasing bait densities and improving bait palatability could potentially improve the efficacy of baiting programs to reduce feral cat populations. Our study provides a framework to measure and evaluate the key elements that contribute to efficacy of pest control programs, and to identify opportunities for improving outcomes of future control programs.

Parasite stress and pathogen avoidance relate to distinct dimensions of political ideology across 30 nations.

People who are more avoidant of pathogens are more politically conservative, as are nations with greater parasite stress. In the current research, we test two prominent hypotheses that have been proposed as explanations for these relationships. The first, which is an intragroup account, holds that these relationships between pathogens and politics are based on motivations to adhere to local norms, which are sometimes shaped by cultural evolution to have pathogen-neutralizing properties. The second, which is an intergroup account, holds that these same relationships are based on motivations to avoid contact with outgroups, who might pose greater infectious disease threats than ingroup members. Results from a study surveying 11,501 participants across 30 nations are more consistent with the intragroup account than with the intergroup account. National parasite stress relates to traditionalism (an aspect of conservatism especially related to adherence to group norms) but not to social dominance orientation (SDO; an aspect of conservatism especially related to endorsements of intergroup barriers and negativity toward ethnic and racial outgroups). Further, individual differences in pathogen-avoidance motives (i.e., disgust sensitivity) relate more strongly to traditionalism than to SDO within the 30 nations.

Reviewing current knowledge in snatch performance and technique: the need for future directions in applied research.

This is a review of current research trends in weightlifting literature relating to the understanding of technique and its role in successful snatch performance. Reference to the world records in the snatch from the 1960s onwards indicates little progress across all weight categories. With such mediocre advances in performance at the International level, there is a need to better understand how snatch technique can improve performance even if only by a small margin. Methods of data acquisition for technical analysis of the snatch have involved mostly 2-dimensional barbell and joint kinematics. Although key variables which play a role in the successful outcome of a snatch lift have been heavily investigated, few studies have combined variables relating both the barbell and the weightlifter in their analyses. This suggests the need for a more detailed approach integrating both barbell-related and weightlifter-related data to enhance understanding of the mechanics of a successful lift. Currently, with the aid of technical advances in motion analysis, data acquisition, and methods of analysis, a more accurate representation of the movement can be provided. Better ways of understanding the key characteristics of technique in the snatch could provide the opportunity for more effective individualized feedback from the coach to the athlete, which should in turn lead to improved performance in competition.

Is starting with the feet out of the water faster in backstroke swimming?

This study aimed to determine if starting with the feet above the water (FAW) in male backstroke swimming resulted in faster start times (15-m time) than when the feet were underwater (FUW). It was hypothesised that setting higher on the wall would generate increased horizontal force and velocity, resulting in quicker starts. Twelve high-level male backstrokers performed three trials of the FAW and FUW techniques. A biomechanical swimming testing system comprising one force plate (1,000 Hz), four lateral-view (100Hz), and five overhead (50Hz) video cameras captured the swimmers' performance. Data for each participant's fastest trial for each technique were collated, grouped, and statistically analysed. Analysis included Wilcoxon, Spearman Rho correlation, and regression analysis. Wilcoxon results revealed a significantly faster start time for the FAW technique (p < 0.01). Peak horizontal force was significantly smaller for FAW (p = 0.02), while take-off horizontal velocity was significantly greater (p = 0.01). Regression analysis indicated take-off horizontal velocity to be a good predictor of start time for both techniques, and the horizontal displacement of the centre of mass for the FAW start.

The Advantages of Flexibility: The Role of Entropy in Crystal Structures Containing C-H···F Interactions.

Molecular crystal structures are often interpreted in terms of strong, structure directing, intermolecular interactions, especially those with distinct geometric signatures such as H-bonds or π-stacking interactions. Other interactions can be overlooked, perhaps because they are weak or lack a characteristic geometry. We show that although the cumulative effect of weak interactions is significant, their deformability also leads to occupation of low energy vibrational energy levels, which provides an additional stabilizing entropic contribution. The entropies of five fluorobenzene derivatives have been calculated by periodic DFT calculations to assess the entropic influence of C-H···F interactions in stabilizing their crystal structures. Calculations reproduce inelastic neutron scattering data and experimental entropies from heat capacity measurements. C-H···F contacts are shown to have force constants which are around half of those of more familiar interactions such as hydrogen bonds, halogen bonds, and C-H···π interactions. This feature, in combination with the relatively high mass of F, means that the lowest energy vibrations in crystalline fluorobenzenes are dominated by C-H···F contributions. C-H···F contacts occur much more frequently than would be expected from their enthalpic contributions alone, but at 150 K, the stabilizing contribution of entropy provides, at -10 to -15 kJ mol-1, a similar level of stabilization to the N-H···N hydrogen bond in ammonia and O-H···O hydrogen bond in water.

The Effect of High Pressure on Polymorphs of a Derivative of Blatter's Radical: Identification of the Structural Signatures of Subtle Phase Transitions.

The effect of pressure on the α and ß polymorphs of a derivative of Blatter's radical, 3-phenyl-1-(pyrid-2-yl)-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl, has been investigated using single-crystal X-ray diffraction to maximum pressures of 5.76 and 7.42 GPa, respectively. The most compressible crystallographic direction in both structures lies parallel to π-stacking interactions, which semiempirical Pixel calculations indicate are also the strongest interactions present. The mechanism of compression in perpendicular directions is determined by void distributions. Discontinuities in the vibrational frequencies observed in Raman spectra measured between ambient pressure and ∼5.5 GPa show that both polymorphs undergo phase transitions, the α phase at 0.8 GPa and the ß phase at 2.1 GPa. The structural signatures of the transitions, which signal the onset of compression of initially more rigid intermolecular contacts, were identified from the trends in the occupied and unoccupied volumes of the unit cell with pressure and in the case of the ß phase by deviations from an ideal model of compression defined by Birch-Murnaghan equations of state.

Adjustable passive stiffness in mouse bladder: regulated by Rho kinase and elevated following partial bladder outlet obstruction.

Detrusor smooth muscle (DSM) contributes to bladder wall tension during filling, and bladder wall deformation affects the signaling system that leads to urgency. The length-passive tension (L-T(p)) relationship in rabbit DSM can adapt with length changes over time and exhibits adjustable passive stiffness (APS) characterized by a L-T(p) curve that is a function of both activation and strain history. Muscle activation with KCl, carbachol (CCh), or prostaglandin E(2) at short muscle lengths can increase APS that is revealed by elevated pseudo-steady-state T(p) at longer lengths compared with prior T(p) measurements at those lengths, and APS generation is inhibited by the Rho Kinase (ROCK) inhibitor H-1152. In the current study, mouse bladder strips exhibited both KCl- and CCh-induced APS. Whole mouse bladders demonstrated APS which was measured as an increase in pressure during passive filling in calcium-free solution following CCh precontraction compared with pressure during filling without precontraction. In addition, CCh-induced APS in whole mouse bladder was inhibited by H-1152, indicating that ROCK activity may regulate bladder compliance during filling. Furthermore, APS in whole mouse bladder was elevated 2 wk after partial bladder outlet obstruction, suggesting that APS may be relevant in diseases affecting bladder mechanics. The presence of APS in mouse bladder will permit future studies of APS regulatory pathways and potential alterations of APS in disease models using knockout transgenetic mice.

Behavior of Occupied and Void Space in Molecular Crystal Structures at High Pressure.

We report a Monte Carlo algorithm for calculation of occupied ("network") and unoccupied ("void") space in crystal structures. The variation of the volumes of the voids and the network of intermolecular contacts with pressure sensitively reveals discontinuities associated with first- and second-order phase transitions, providing insights into the effect of compression (and, in principle, other external stimuli) at a level between those observed in individual contact distances and the overall unit cell dimensions. The method is shown to be especially useful for the correlation of high-pressure crystallographic and spectroscopic data, illustrated for naphthalene, where a phase transition previously detected by vibrational spectroscopy, and debated in the literature for over 80 years, has been revealed unambiguously in crystallographic data for the first time. Premonitory behavior before a phase transition and crystal collapse at the end of a compression series has also been detected. The network and void volumes for 129 high-pressure studies taken from the Cambridge Structural Database (CSD) were fitted to equation of state to show that networks typically have bulk moduli between 40 and 150 GPa, while those of voids fall into a much smaller range, 2-5 GPa. These figures are shown to reproduce the narrow range of overall bulk moduli of molecular solids (ca. 5-20 GPa). The program, called CellVol, has been written in Python using the CSD Python API and can be run through the command line or through the Cambridge Crystallographic Data Centre's Mercury interface.

A first-order phase transition in Blatter's radical at high pressure.

The crystal structure of Blatter's radical (1,3-diphenyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl) has been investigated between ambient pressure and 6.07 GPa. The sample remains in a compressed form of the ambient-pressure phase up to 5.34 GPa, the largest direction of strain being parallel to the direction of π-stacking interactions. The bulk modulus is 7.4 (6) GPa, with a pressure derivative equal to 9.33 (11). As pressure increases, the phenyl groups attached to the N1 and C3 positions of the triazinyl moieties of neighbouring pairs of molecules approach each other, causing the former to begin to rotate between 3.42 to 5.34 GPa. The onset of this phenyl rotation may be interpreted as a second-order phase transition which introduces a new mode for accommodating pressure. It is premonitory to a first-order isosymmetric phase transition which occurs on increasing pressure from 5.34 to 5.54 GPa. Although the phase transition is driven by volume minimization, rather than relief of unfavourable contacts, it is accompanied by a sharp jump in the orientation of the rotation angle of the phenyl group. DFT calculations suggest that the adoption of a more planar conformation by the triazinyl moiety at the phase transition can be attributed to relief of intramolecular H...H contacts at the transition. Although no dimerization of the radicals occurs, the π-stacking interactions are compressed by 0.341 (3) Šbetween ambient pressure and 6.07 GPa.

Using three-dimensional kinematics to identify feedback for the Snatch: a case study.

This case study evaluated the importance of peak bar velocity and starting posture adopted by a novice weightlifter to the outcome of a Snatch lift. Multiple observations of both successful and unsuccessful attempts were captured using 3D motion analysis (VICON MX: 500 Hz). The following data analysis was then used to derive feedback. In total, 133 attempts of loads ranging from 75 to 100% of 1 repetition maximum (1RM) were performed by the subject (age = 25 years, stature = 171 cm, mass = 74.8 kg, Snatch 1RM = 80 kg). Variables included peak bar velocity, pelvis, hip, knee and ankle joint angles at the starting position for the right side and the difference between (left minus right) sides. No main effects for load, success, or their interactions were found for peak bar velocity. Starting position kinematics were mostly nonsignificant between the outcome of Snatch attempts. Right ankle joint angle was the only exception, where unsuccessful attempts displayed greater (p = 0.0228) dorsiflexion. A more comprehensive finding was achieved through the partition modeling; this analysis provided valuable insight and coaching feedback for the subject in relation to his lower body kinematics at the starting position. Furthermore, the accuracy of this feedback was verified using a holdback data set. Specifically, anterior pelvic tilt (>17.6°) and hip joint (<89.6°) angle were identified as the key features to increasing the likelihood of success. In conclusion, this case study outlines a method of data collection and analysis to assist coaching feedback for an individual.

Morphology of bony callus growth in healing of a sheep tibial osteotomy.

Long bone fractures typically heal via formation of an external callus, which helps stabilise the bone fragments. Callus composition and morphology influence the mechanical environment, which in turn regulates the progression of healing. Therefore characterising callus development over time is crucial in understanding this mechanobiological regulation. Although bony callus is often assumed to grow towards the fracture from either side, this is not consistent with observations from large animal studies and clinical cases. Therefore, we sought to quantify the morphology of bony callus over time in a large animal model. Sheep tibiae were x-rayed weekly over eight weeks following an osteotomy (n=5), with fixation allowing up to 10% axial displacement under normal weight-bearing. After scaling radiographs by known landmarks and normalising greyscales, bony callus boundaries were defined by manual segmentation. The lateral callus area and coordinates of its centroid were calculated from each image. The external callus initially formed adjacent to the osteotomy site. Over the first four weeks, callus growth from its outer surfaces was characterised by its centre of area moving outwards and away from the osteotomy, on both proximal and distal fragments. Subsequent weeks showed consolidation and resorption from the outer surface of the callus. Our approach allowed bony callus development to be tracked in individuals throughout healing. Contrary to the view that periosteal bone formation originates distant from the fracture, our data showed bony callus adjacent to the defect from early stages, followed by approximately concentric growth. This discrepancy highlights the need for data specific to experimental conditions, and particularly early stages of healing, for evaluating theoretical models of mechanical regulation.

Cyclic strain disrupts endothelial network formation on Matrigel.

Most forms of tissue healing depend critically on revascularisation. In soft tissues and in vitro, mechanical stimuli have been shown to promote vessel-forming activity. However, in bone defects, increased interfragmentary motion impairs vascular regeneration. Because these effects seem contradictory, we aimed to determine whether a range of mechanical stimuli exists in which angiogenesis is favoured. A series of cyclic strain magnitudes were applied to a Matrigel-based "tube formation" assay and the total lengths of networks formed by human microvascular endothelial cells measured at 24 h. Network lengths were reduced at all strain levels, compared to unstretched controls. However, the levels of pro-angiogenic matrix metalloproteases-2 and -9 in the corresponding conditioned media were unchanged by strain, and vascular endothelial growth factor was uniformly elevated in stretched conditions. By repeating the assay with the addition of conditioned media from mesenchymal stem cells cultivated in similar conditions, paracrine stimuli were shown to increase network lengths, but not to alter the negative effect of cyclic stretching. Together, these results demonstrate that directly applied periodic strains can inhibit endothelial organisation in vitro, and suggest that this may be due to physical disruption rather than biochemical modulation. Most importantly, the results indicate that the straining of endothelial cells and their assembly into vascular-like structures must be studied simultaneously to adequately characterise the mechanical influence on vessel formation.

Reliability of the Ekblom soccer-specific endurance test.

The aim of this study was to explore and quantify measurement reliability of the Ekblom endurance test. Experienced university soccer players (n = 19; age = 20.5 +/- 2.5 years; mass = 80.4 +/- 9.8 kg; and stature = 179.0 +/- 6.0 cm) completed the Ekblom endurance test on 3 separate occasions. Time to complete trial 1 (549 +/- 26 seconds) and trial 2 (547 +/- 26 seconds) was analyzed, and despite no significant difference (F1,18 = 4.119, p = 0.057, etaP = 0.186) between trials, some evidence of systematic bias was observed in the data. Therefore, trial 2 data were compared with those of trial 3 (548 +/- 27 seconds), with trial 1 data removed. The subsequent analysis (F1,18 = 0.740, p = 0.401, etaP = 0.039) showed a reduction in the risk of making a type II error when compared with the previous analysis. From the reliability analyses (3,1 intraclass correlation = 0.983, SEM = +/-3 seconds, smallest worthwhile change = 5 seconds, standard error of prediction [95% confidence intervals] = +/- 9 seconds), a high level of measurement reliability was observed and the sensitivity of the test to monitor changes was "good." In summary, it was shown that a test that involves a variety of soccer-specific forms of locomotion can be highly reliable and sensitive to detect change. In light of the systematic bias found, we do, however, recommend a familiarization session to be scheduled before the introduction of this test.

Computational simulation of bone fracture healing under inverse dynamisation.

Adaptive finite element models have allowed researchers to test hypothetical relationships between the local mechanical environment and the healing of bone fractures. However, their predictive power has not yet been demonstrated by testing hypotheses ahead of experimental testing. In this study, an established mechano-biological scheme was used in an iterative finite element simulation of sheep tibial osteotomy healing under a hypothetical fixation regime, "inverse dynamisation". Tissue distributions, interfragmentary movement and stiffness across the fracture site were compared between stiff and flexible fixation conditions and scenarios in which fixation stiffness was increased at a discrete time-point. The modelling work was conducted blind to the experimental study to be published subsequently. The simulations predicted the fastest and most direct healing under constant stiff fixation, and the slowest healing under flexible fixation. Although low fixation stiffness promoted more callus formation prior to bridging, this conferred little additional stiffness to the fracture in the first 5 weeks. Thus, while switching to stiffer fixation facilitated rapid subsequent bridging of the fracture, no advantage of inverse dynamisation could be demonstrated. In vivo data remains necessary to conclusively test this treatment protocol and this will, in turn, provide an evaluation of the model's performance. The publication of both hypotheses and their computational simulation, prior to experimental testing, offers an appealing means to test the predictive power of mechano-biological models.

External kinetics of the kettlebell snatch in amateur lifters.

BACKGROUND: Kettlebell lifting has gained increased popularity as both a form of resistance training and as a sport, despite the paucity of literature validating its use as a training tool. Kettlebell sport requires participants to complete the kettlebell snatch continuously over prolonged periods of time. Kettlebell sport and weightlifting involve similar exercises, however, their traditional uses suggest they are better suited to training different fitness qualities. This study examined the three-dimensional ground reaction force (GRF) and force applied to the kettlebell over a 6 min kettlebell snatch set in 12 kettlebell-trained males. METHODS: During this set, VICON was used to record the kettlebell trajectory with nine infrared cameras while the GRF of each leg was recorded with a separate AMTI force plate. Over the course of the set, an average of 13.9 ± 3.3 repetitions per minute were performed with a 24 kg kettlebell. Significance was evaluated with a two-way ANOVA and paired t-tests, whilst Cohen's F (ESF) and Cohen's D (ESD) were used to determine the magnitude. RESULTS: The applied force at the point of maximum acceleration was 814 ± 75 N and 885 ± 86 N for the downwards and upwards phases, respectively. The absolute peak resultant bilateral GRF was 1,746 ± 217 N and 1,768 ± 242 N for the downwards and upwards phases, respectively. Bilateral GRF of the first and last 14 repetitions was found to be similar, however there was a significant difference in the peak applied force (F (1.11) = 7.42, p = 0.02, ESF = 0.45). Unilateral GRF was found have a significant difference for the absolute anterior-posterior (F (1.11) = 885.15, p < 0.0001, ESF = 7) and medio-lateral force vectors (F (1.11) = 5.31, p = 0.042, ESF = 0.67). DISCUSSION: Over the course of a single repetition there were significant differences in the GRF and applied force at multiple points of the kettlebells trajectory. The kettlebell snatch loads each leg differently throughout a repetition and performing the kettlebell snatch for 6 min will result in a reduction in peak applied force.

Mediation of biomaterial-cell interactions by adsorbed proteins: a review.

An appropriate cellular response to implanted surfaces is essential for tissue regeneration and integration. It is well described that implanted materials are immediately coated with proteins from blood and interstitial fluids, and it is through this adsorbed layer that cells sense foreign surfaces. Hence, it is the adsorbed proteins, rather than the surface itself, to which cells initially respond. Diverse studies using a range of materials have demonstrated the pivotal role of extracellular adhesion proteins--fibronectin and vitronectin in particular--in cell adhesion, morphology, and migration. These events underlie the subsequent responses required for tissue repair, with the nature of cell surface interactions contributing to survival, growth, and differentiation. The pattern in which adhesion proteins and other bioactive molecules adsorb thus elicits cellular reactions specific to the underlying physicochemical properties of the material. Accordingly, in vitro studies generally demonstrate favorable cell responses to charged, hydrophilic surfaces, corresponding to superior adsorption and bioactivity of adhesion proteins. This review illustrates the mediation of cell responses to biomaterials by adsorbed proteins, in the context of osteoblasts and selected materials used in orthopedic implants and bone tissue engineering. It is recognized, however, that the periimplant environment in vivo will differ substantially from the cell-biomaterial interface in vitro. Hence, one of the key issues yet to be resolved is that of the interface composition actually encountered by osteoblasts within the sequence of inflammation and bone regeneration.

Effects of strain artefacts arising from a pre-defined callus domain in models of bone healing mechanobiology.

Iterative computational models have been used to investigate the regulation of bone fracture healing by local mechanical conditions. Although their predictions replicate some mechanical responses and histological features, they do not typically reproduce the predominantly radial hard callus growth pattern observed in larger mammals. We hypothesised that this discrepancy results from an artefact of the models' initial geometry. Using axisymmetric finite element models, we demonstrated that pre-defining a field of soft tissue in which callus may develop introduces high deviatoric strains in the periosteal region adjacent to the fracture. These bone-inhibiting strains are not present when the initial soft tissue is confined to a thin periosteal layer. As observed in previous healing models, tissue differentiation algorithms regulated by deviatoric strain predicted hard callus forming remotely and growing towards the fracture. While dilatational strain regulation allowed early bone formation closer to the fracture, hard callus still formed initially over a broad area, rather than expanding over time. Modelling callus growth from a thin periosteal layer successfully predicted the initiation of hard callus growth close to the fracture site. However, these models were still susceptible to elevated deviatoric strains in the soft tissues at the edge of the hard callus. Our study highlights the importance of the initial soft tissue geometry used for finite element models of fracture healing. If this cannot be defined accurately, alternative mechanisms for the prediction of early callus development should be investigated.

Mechanical tension as a driver of connective tissue growth in vitro.

We propose the progressive mechanical expansion of cell-derived tissue analogues as a novel, growth-based approach to in vitro tissue engineering. The prevailing approach to producing tissue in vitro is to culture cells in an exogenous "scaffold" that provides a basic structure and mechanical support. This necessarily pre-defines the final size of the implantable material, and specific signals must be provided to stimulate appropriate cell growth, differentiation and matrix formation. In contrast, surgical skin expansion, driven by increments of stretch, produces increasing quantities of tissue without trauma or inflammation. This suggests that connective tissue cells have the innate ability to produce growth in response to elevated tension. We posit that this capacity is maintained in vitro, and that order-of-magnitude growth may be similarly attained in self-assembling cultures of cells and their own extracellular matrix. The hypothesis that growth of connective tissue analogues can be induced by mechanical expansion in vitro may be divided into three components: (1) tension stimulates cell proliferation and extracellular matrix synthesis; (2) the corresponding volume increase will relax the tension imparted by a fixed displacement; (3) the repeated application of static stretch will produce sustained growth and a tissue structure adapted to the tensile loading. Connective tissues exist in a state of residual tension, which is actively maintained by resident cells such as fibroblasts. Studies in vitro and in vivo have demonstrated that cellular survival, reproduction, and matrix synthesis and degradation are regulated by the mechanical environment. Order-of-magnitude increases in both bone and skin volume have been achieved clinically through staged expansion protocols, demonstrating that tension-driven growth can be sustained over prolonged periods. Furthermore, cell-derived tissue analogues have demonstrated mechanically advantageous structural adaptation in response to applied loading. Together, these data suggest that a program of incremental stretch constitutes an appealing way to replicate tissue growth in cell culture, by harnessing the constituent cells' innate mechanical responsiveness. In addition to offering a platform to study the growth and structural adaptation of connective tissues, tension-driven growth presents a novel approach to in vitro tissue engineering. Because the supporting structure is secreted and organised by the cells themselves, growth is not restricted by a "scaffold" of fixed size. This also minimises potential adverse reactions to exogenous materials upon implantation. Most importantly, we posit that the growth induced by progressive stretch will allow substantial volumes of connective tissue to be produced from relatively small initial cell numbers.