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1.
Adv Sci (Weinh) ; : e2400250, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554396

RESUMO

Porous materials with sound absorption and load-bearing capabilities are in demand in engineering fields like aviation and rail transportation. However, achieving both properties simultaneously is challenging due to the trade-off between interconnected pores for sound absorption and mechanical strength. Inspired by quilling art, a novel design using spiral material formed by rolling planar materials into helical structures is proposed. Experimental results show high structural strength through self-locking mechanisms, while double porosities from interlayer spiral slits and aligned submillimeter pores provide excellent sound absorption. These spiral sheets surpass foam aluminum in specific strength (up to 5.1 MPa) and approach aerogels in sound absorption (average coefficient of 0.93 within 0-6400 Hz). With its adaptability to various planar materials, this spiral design allows for hybrid combinations of different materials for multi-functionality, paving the way for designing advanced, lightweight porous materials for broad applications.

2.
Langmuir ; 40(2): 1555-1566, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38051264

RESUMO

Liquid-filled capillary tubes are a kind of standard component in life science (e.g., blood vessels, interstitial pores, and plant vessels) and engineering (e.g., MEMS microchannel resonators, heat pipe wicks, and water-saturated soils). Under sufficiently low temperatures, the liquid in a capillary tube undergoes phase transition, forming an ice nucleus randomly on its inner wall. However, how an ice layer forms from the nucleus and then expands, either axially or radially to the tube inner wall, remains obscure. We demonstrated, both experimentally and theoretically, that axial freezing along the inner wall of a water-filled capillary tube occurs way ahead of radial freezing, at a nearly constant velocity 3 orders in magnitude faster than the latter. Rapid release of latent heat during axial freezing was identified as the determining factor for the short duration of recalescence, resulting in an exponential rise of the supercooling temperature from ice nucleation via axial freezing to radial freezing. The profile of the ice-water interface is strongly dependent upon the length-to-radius ratio of the capillary tube and the supercooling degree at ice nucleation. The results obtained in this study bridge the knowledge gap between the classical nucleation theory and the Stefan solution of phase transition.

3.
Adv Sci (Weinh) ; 10(35): e2302421, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37849221

RESUMO

Dynamically evolving adhesions between cells and extracellular matrix (ECM) transmit time-varying signals that control cytoskeletal dynamics and cell fate. Dynamic cell adhesion and ECM stiffness regulate cellular mechanosensing cooperatively, but it has not previously been possible to characterize their individual effects because of challenges with controlling these factors independently. Therefore, a DNA-driven molecular system is developed wherein the integrin-binding ligand RGD can be reversibly presented and removed to achieve cyclic cell attachment/detachment on substrates of defined stiffness. Using this culture system, it is discovered that cyclic adhesion accelerates F-actin kinetics and nuclear mechanosensing in human mesenchymal stem cells (hMSCs), with the result that hysteresis can completely change how hMSCs transduce ECM stiffness. Results are dramatically different from well-known results for mechanotransduction on static substrates, but are consistent with a mathematical model of F-actin fragments retaining structure following loss of integrin ligation and participating in subsequent repolymerization. These findings suggest that cyclic integrin-mediated adhesion alters the mechanosensing of ECM stiffness by hMSCs through transient, hysteretic memory that is stored in F-actin.


Assuntos
Actinas , Integrinas , Humanos , Adesão Celular/fisiologia , Integrinas/metabolismo , Actinas/análise , Actinas/metabolismo , Mecanotransdução Celular , Matriz Extracelular/metabolismo
4.
Materials (Basel) ; 16(19)2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37834741

RESUMO

Inspired by material hybrid design, novel hybrid sandwich shells were developed by filling a corrugated cylindrical structure with aluminum foam to achieve higher energy absorption performance. The crushing behavior of the foam-filled corrugated sandwich cylindrical shells (FFCSCSs) was investigated using theoretical and numerical methods. Numerical results revealed a significant enhancement in the energy absorption of FFCSCSs under axial compression, showcasing a maximum specific energy absorption of 60 kJ/kg. The coupling strengthening effect is highly pronounced, with a maximum value of F¯c/F¯ reaching up to 40%. The mechanism underlying this phenomenon can be approached from two perspectives. Firstly, the intrusion of folds into the foam insertions allows for more effective foam compression, maximizing its energy absorption capacity. Secondly, foam causes the folds to bend upwards, intensifying the mutual compression between the folds. This coupling mechanism was further investigated with a focus on analyzing the influence of parameters such as the relative density of the foam, the wall thickness of the sandwich shell, and the material properties. Moreover, a theoretical model was developed to accurately predict the mean crushing force of the FFCSCSs. Based on this model, the influence of various variables on the crushing behavior of the structure was thoroughly investigated through parametric studies.

5.
Materials (Basel) ; 16(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37297220

RESUMO

Thin structural elements such as large-scale covering plates of aerospace protection structures and vertical stabilizers of aircraft are strongly influenced by gravity (and/or acceleration); thus, exploring how the mechanical behaviors of such structures are affected by gravitational field is necessary. Built upon a zigzag displacement model, this study establishes a three-dimensional vibration theory for ultralight cellular-cored sandwich plates subjected to linearly varying in-plane distributed loads (due to, e.g., hyper gravity or acceleration), with the cross-section rotation angle induced by face sheet shearing accounted for. For selected boundary conditions, the theory enables quantifying the influence of core type (e.g., close-celled metal foams, triangular corrugated metal plates, and metal hexagonal honeycombs) on fundamental frequencies of the sandwich plates. For validation, three-dimensional finite element simulations are carried out, with good agreement achieved between theoretical predictions and simulation results. The validated theory is subsequently employed to evaluate how the geometric parameters of metal sandwich core and the mixture of metal cores and composite face sheets influence the fundamental frequencies. Triangular corrugated sandwich plate possesses the highest fundamental frequency, irrespective of boundary conditions. For each type of sandwich plate considered, the presence of in-plane distributed loads significantly affects its fundamental frequencies and modal shapes.

6.
Adv Drug Deliv Rev ; 194: 114722, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36738968

RESUMO

Mechanotherapy is proposed as a new option for cancer treatment. Increasing evidence suggests that characteristic differences are present in the nuclear mechanics and mechanotransduction of cancer cells compared with those of normal cells. Recent advances in understanding nuclear mechanics and mechanotransduction provide not only further insights into the process of malignant transformation but also useful references for developing new therapeutic approaches. Herein, we present an overview of the alterations of nuclear mechanics and mechanotransduction in cancer cells and highlight their implications in cancer mechanotherapy.


Assuntos
Mecanotransdução Celular , Neoplasias , Humanos , Núcleo Celular
7.
Acta Biomater ; 155: 423-435, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36372152

RESUMO

Brain tissue is considered to be biphasic, with approximately 80% liquid and 20% solid matrix, thus exhibiting viscoelasticity due to rearrangement of the solid matrix and poroelasticity due to fluid migration within the solid matrix. However, how to distinguish poroelastic and viscoelastic effects in brain tissue remains challenging. In this study, we proposed a method of unconfined compression-isometric hold to measure the force versus time relaxation curves of porcine brain tissue samples with systematically varied sample lengths. Upon scaling the measured relaxation force and relaxation time with different length-dependent physical quantities, we successfully distinguished the poroelasticity and viscoelasticity of the brain tissue. We demonstrated that during isometric hold, viscoelastic relaxation dominated the mechanical behavior of brain tissue in the short-time regime, while poroelastic relaxation dominated in the long-time regime. Furthermore, compared with poroelastic relaxation, viscoelastic relaxation was found to play a more dominant role in the mechanical response of porcine brain tissue. We then evaluated the differences between poroelastic and viscoelastic effects for both porcine and human brain tissue. Because of the draining of pore fluid, the Young's moduli in poroelastic relaxation were lower than those in viscoelastic relaxation; brain tissue changed from incompressible during viscoelastic relaxation to compressible during poroelastic relaxation, resulting in reduced Poisson ratios. This study provides new insights into the physical mechanisms underlying the roles of viscoelasticity and poroelasticity in brain tissue. STATEMENT OF SIGNIFICANCE: Although the poroviscoelastic model had been proposed to characterize brain tissue mechanical behavior, it is difficult to distinguish the poroelastic and viscoelastic behaviors of brain tissue. The study distinguished viscoelasticity and poroelasticity of brain tissue with time scales and then evaluated the differences between poroelastic and viscoelastic effects for both porcine and human brain tissue, which helps to accurate selection of constitutive models suitable for application in certain situations (e.g., pore-dominant and viscoelastic-dominant deformation).


Assuntos
Encéfalo , Modelos Biológicos , Humanos , Animais , Suínos , Elasticidade , Fenômenos Biomecânicos , Módulo de Elasticidade , Viscosidade , Estresse Mecânico
8.
Nat Commun ; 13(1): 6854, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369425

RESUMO

During mesenchymal development, the sources of mechanical forces transduced by cells transition over time from predominantly cell-cell interactions to predominantly cell-extracellular matrix (ECM) interactions. Transduction of the associated mechanical signals is critical for development, but how these signals converge to regulate human mesenchymal stem cells (hMSCs) mechanosensing is not fully understood, in part because time-evolving mechanical signals cannot readily be presented in vitro. Here, we established a DNA-driven cell culture platform that could be programmed to present the RGD peptide from fibronectin, mimicking cell-ECM interactions, and the HAVDI peptide from N-cadherin, mimicking cell-cell interactions, through DNA hybridization and toehold-mediated strand displacement reactions. The platform could be programmed to mimic the evolving cell-ECM and cell-cell interactions during mesenchymal development. We applied this platform to reveal that RGD/integrin ligation promoted cofilin phosphorylation, while HAVDI/N-cadherin ligation inhibited cofilin phosphorylation. Cofilin phosphorylation upregulated perinuclear apical actin fibers, which deformed the nucleus and thereby induced YAP nuclear localization in hMSCs, resulting in subsequent osteogenic differentiation. Our programmable culture platform is broadly applicable to the study of dynamic, integrated mechanobiological signals in development, healing, and tissue engineering.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Humanos , Integrinas/metabolismo , Caderinas/metabolismo , Fosforilação , Adesivos/metabolismo , Fatores de Despolimerização de Actina/metabolismo , Células-Tronco Mesenquimais/metabolismo , Diferenciação Celular , Matriz Extracelular/metabolismo , DNA/metabolismo
9.
J Mech Behav Biomed Mater ; 135: 105432, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36115174

RESUMO

Blockage of ureter caused by kidney stone, accompanied by severe pain/infections, is a high incidence urinary tract disease that has received extensive attention. Currently, in clinics, a kidney stone with diameter less than ∼5 mm is considered capable of passing through ureter. However, this critical size (∼5 mm) is empirically based, lacking quantitative analysis. In this study, we proposed a stone-ureter interaction model to quantificationally estimate the critical size of kidney stone passing through ureter. We revealed that the critical size of kidney stone is related to ureter size, about 11%-22% larger than the inner diameter of ureter. Further, based upon the Winkler elastic foundation beam model, we developed a simplified stone-ureter interaction model to evaluate how this critical size is dependent upon the stiffness of ureter and the surface roughness of kidney stone. The proposed model may help urologists improve the accuracy of personalized diagnosis and treatment.


Assuntos
Cálculos Renais , Ureter , Humanos , Cálculos Renais/terapia
10.
Biophys J ; 121(20): 3917-3926, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36045574

RESUMO

Acoustic transduction by plants has been proposed as a mechanism to enable just-in-time up-regulation of metabolically expensive defensive compounds. Although the mechanisms by which this "hearing" occurs are unknown, mechanosensation by elongated plant hair cells known as trichomes is suspected. To evaluate this possibility, we developed a theoretical model to evaluate the acoustic radiation force that an elongated cylinder can receive in response to sounds emitted by animals, including insect herbivores, and applied it to the long, cylindrical stem trichomes of the tomato plant Solanum lycopersicum. Based on perturbation theory and validated by finite element simulations, the model quantifies the effects of viscosity and frequency on this acoustic radiation force. Results suggest that acoustic emissions from certain animals, including insect herbivores, may produce acoustic radiation force sufficient to trigger stretch-activated ion channels.


Assuntos
Solanum lycopersicum , Animais , Solanum lycopersicum/fisiologia , Tricomas , Acústica
11.
Phys Rev E ; 106(1-1): 014405, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35974577

RESUMO

During descent, a single-winged maple seed (samara) can naturally reach a delicate equilibrium state, stable autorotation, before landing. This article reveals the intrinsic equilibrium of a particular type of samaras in terms of measurable aerodynamic and geometric parameters. To this end, we conducted a series of in situ measurements for the rate of vertical descent (exclusive of crosswind) of an autorotating samara in a natural range of samara sizes and masses. We then extended the range of size and mass by introducing artificial samaras, with discrete mass elements purposely designed to approximate the asymmetrical and nonuniform distribution of mass found with natural samaras. Based on the widened range, a fundamental nondimensional correlation of dynamic pressure and disc loading was generalized, where all stable autorotation descent profiles collapse to a single descent characteristic curve, irrespective of the size and mass of the natural and artificial samara's specimens. Results reveal that for stably autorotating (both natural and artificial) samaras, their terminal descent velocity (expressed as dynamic pressure) and disc loading attained equilibrium at a value that is inversely proportional to the coefficient of lift.

12.
Nat Mater ; 21(9): 1081-1090, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35817964

RESUMO

How cells sense tissue stiffness to guide cell migration is a fundamental question in development, fibrosis and cancer. Although durotaxis-cell migration towards increasing substrate stiffness-is well established, it remains unknown whether individual cells can migrate towards softer environments. Here, using microfabricated stiffness gradients, we describe the directed migration of U-251MG glioma cells towards less stiff regions. This 'negative durotaxis' does not coincide with changes in canonical mechanosensitive signalling or actomyosin contractility. Instead, as predicted by the motor-clutch-based model, migration occurs towards areas of 'optimal stiffness', where cells can generate maximal traction. In agreement with this model, negative durotaxis is selectively disrupted and even reversed by the partial inhibition of actomyosin contractility. Conversely, positive durotaxis can be switched to negative by lowering the optimal stiffness by the downregulation of talin-a key clutch component. Our results identify the molecular mechanism driving context-dependent positive or negative durotaxis, determined by a cell's contractile and adhesive machinery.


Assuntos
Actomiosina , Fenômenos Biomecânicos , Movimento Celular
13.
Matter ; 4(9): 2886-2901, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34746749

RESUMO

Mechanical deformation of human skin provides essential information about human motions, muscle stretching, vocal fold vibration, and heart rates. Monitoring these activities requires the measurement of strains at different levels. Herein, we report a wearable wide-range strain sensor based on conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). A bioinspired bilayer structure was constructed to enable a wide-range strain sensing (1%~100%). Besides, hydrogel was chosen as the biological- and mechanical-compatible interface layer with the human skin. Finally, we demonstrated that the strain sensor is capable of monitoring various strain-related activities, including subtle skin deformation (pulse and phonation), mid-level body stretch (swallowing and facial expressions), and substantial joint movement (elbow bending).

14.
Nat Commun ; 12(1): 6229, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711824

RESUMO

Mesenchymal stem cells adopt differentiation pathways based upon cumulative effects of mechanosensing. A cell's mechanical microenvironment changes substantially over the course of development, beginning from the early stages in which cells are typically surrounded by other cells and continuing through later stages in which cells are typically surrounded by extracellular matrix. How cells erase the memory of some of these mechanical microenvironments while locking in memory of others is unknown. Here, we develop a material and culture system for modifying and measuring the degree to which cells retain cumulative effects of mechanosensing. Using this system, we discover that effects of the RGD adhesive motif of fibronectin (representative of extracellular matrix), known to impart what is often termed "mechanical memory" in mesenchymal stem cells via nuclear YAP localization, are erased by the HAVDI adhesive motif of the N-cadherin (representative of cell-cell contacts). These effects can be explained by a motor clutch model that relates cellular traction force, nuclear deformation, and resulting nuclear YAP re-localization. Results demonstrate that controlled storage and removal of proteins associated with mechanical memory in mesenchymal stem cells is possible through defined and programmable material systems.


Assuntos
Caderinas/metabolismo , Núcleo Celular/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proteínas de Sinalização YAP/metabolismo , Motivos de Aminoácidos , Fenômenos Biomecânicos , Caderinas/química , Caderinas/genética , Núcleo Celular/química , Núcleo Celular/genética , Humanos , Células-Tronco Mesenquimais/química , Transporte Proteico
15.
ACS Omega ; 6(33): 21646-21654, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34471768

RESUMO

Liquid-filled porous materials exist widely in nature and engineering fields, with the diffusion of substances in them playing an important role in system functions. Although surface evaporation is often inevitable in practical scenarios, the evaporation effects on diffusion behavior in liquid-filled porous materials have not been well explored yet. In this work, we performed noninvasive diffusion imaging experiments to observe the diffusion process of erioglaucine disodium salt dye in a liquid-filled nitrocellulose membrane under a wide range of relative humidities (RHs). We found that evaporation can significantly accelerate the diffusion rate and alter concentration distribution compared with the case without evaporation. We explained the accelerated diffusion phenomenon by the mechanism that evaporation would induce a weak flow in liquid-filled porous materials, which leads to convective diffusion, i.e., evaporation-induced flow and diffusion (EIFD). Based on the EIFD mechanism, we proposed a convective diffusion model to quantitatively predict the diffusion process in liquid-filled porous materials under evaporation and experimentally validated the model. Introducing the dimensionless Peclet (P e) number to measure the relative contribution of the evaporation effect to pure molecular diffusion, we demonstrated that even at a high RH of 95%, where the evaporation effect is usually assumed negligible in common sense, the evaporation-induced diffusion still overwhelms the molecular diffusion. The flow velocity induced by evaporation in liquid-filled porous materials was found to be 0.4-5 µm/s, comparable to flow in many biological and biomedical systems. The present analysis may help to explain the driving mechanism of tissue perfusion and provide quantitative analysis or inspire new control methods of flow and material exchange in numerous cutting-edge technologies, such as paper-based diagnostics, hydrogel-based flexible electronics, evaporation-induced electricity generation, and seawater purification.

16.
Biophys J ; 120(17): 3764-3775, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34280368

RESUMO

Although coupling between cardiomyocytes and myofibroblasts is well known to affect the physiology and pathophysiology of cardiac tissues across species, relating these observations to humans is challenging because the effect of this coupling varies across species and because the sources of these effects are not known. To identify the sources of cross-species variation, we built upon previous mathematical models of myofibroblast electrophysiology and developed a mechanoelectrical model of cardiomyocyte-myofibroblast interactions as mediated by electrotonic coupling and transforming growth factor-ß1. The model, as verified by experimental data from the literature, predicted that both electrotonic coupling and transforming growth factor-ß1 interaction between myocytes and myofibroblast prolonged action potential in rat myocytes but shortened action potential in human myocytes. This variance could be explained by differences in the transient outward K+ current associated with differential Kv4.2 gene expression across species. Results are useful for efforts to extrapolate the results of animal models to the predicted effects in humans and point to potential therapeutic targets for fibrotic cardiomyopathy.


Assuntos
Miócitos Cardíacos , Miofibroblastos , Potenciais de Ação , Animais , Diferenciação Celular , Células Cultivadas , Fibrose , Miócitos Cardíacos/patologia , Miofibroblastos/patologia , Ratos , Fator de Crescimento Transformador beta1
17.
Macromol Rapid Commun ; 42(14): e2100147, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34051002

RESUMO

Hydrogels are commonly doped with stiff nanoscale fillers to endow them with the strength and stiffness needed for engineering applications. Although structure-property relations for many polymer matrix nanocomposites are well established, modeling the new generation of hydrogel nanocomposites requires the study of processing-structure-property relationships because subtle differences in chemical kinetics during their synthesis can cause nearly identical hydrogels to have dramatically different mechanical properties. The authors therefore assembled a framework to relate synthesis conditions (including hydrogel and nanofiller mechanical properties and light absorbance) to gelation kinetics and mechanical properties. They validated the model against experiments on a graphene oxide (GO) doped oligo (ethylene glycol) diacrylate (OEGDA), a system in which, in apparent violation of laws from continuum mechanics, doping can reduce rather than increase the stiffness of the resulting hydrogel nanocomposites. Both model and experiment showed a key role light absorbance-dominated gelation kinetics in determining nanocomposite mechanical properties in conjunction with nanofiller reinforcement, with the nanofiller's attenuation of chemical kinetics sometimes outweighing stiffening effects to explain the observed, anomalous loss of stiffness. By bridging the chemical kinetics and mechanics of nanocomposite hydrogels, the authors' modeling framework shows promise for broad applicability to design of hydrogel nanocomposites.


Assuntos
Nanocompostos , Hidrogéis , Polímeros
18.
Small ; 17(17): e2007325, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33705588

RESUMO

Janus particles with asymmetric crystals show great importance in optoelectronics and photocatalysis, but their synthesis usually requires complicated procedures. Here, an unexpected Janus vitrification phenomenon is observed in a droplet caused by the Leidenfrost effect at a cryogenic temperature, which is commonly regarded as symmetric. The Leidenfrost phenomenon levitates the droplet when it comes in contact with liquid nitrogen causing different cooling conditions on the droplet's top and bottom surfaces. It induces asymmetric crystallization in the droplet, forming a Janus vitrified particle with an asymmetric crystallization borderline after cooling, as further evidenced by cryotransmission electron microscopy (cryo-TEM) experiments. Theoretical analysis and experimental study indicate that the position of the asymmetric crystallization borderline is determined by the droplet radius and density, and the observation window of asymmetric crystallization borderline is determined by the chemical concentration. The finding reveals the asymmetric crystallization phenomenon in droplet vitrification for the first time, and provides a new insight for creating Janus particles through the Leidenfrost phenomenon.

19.
Materials (Basel) ; 14(3)2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33498941

RESUMO

Ultralight sandwich constructions with corrugated channel cores (i.e., periodic fluid-through wavy passages) are envisioned to possess multifunctional attributes: simultaneous load-carrying and heat dissipation via active cooling. Titanium alloy (Ti-6Al-4V) corrugated-channel-cored sandwich panels (3CSPs) with thin face sheets and core webs were fabricated via the technique of selective laser melting (SLM) for enhanced shear resistance relative to other fabrication processes such as vacuum brazing. Four-point bending responses of as-fabricated 3CSP specimens, including bending resistance and initial collapse modes, were experimentally measured. The bending characteristics of the 3CSP structure were further explored using a combined approach of analytical modeling and numerical simulation based on the method of finite elements (FE). Both the analytical and numerical predictions were validated against experimental measurements. Collapse mechanism maps of the 3CSP structure were subsequently constructed using the analytical model, with four collapse modes considered (face-sheet yielding, face-sheet buckling, core yielding, and core buckling), which were used to evaluate how its structural geometry affects its collapse initiation mode.

20.
Adv Healthc Mater ; 10(8): e2001856, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33511795

RESUMO

Natural extracellular matrix (ECM) mostly has a fibrous structure that supports and mechanically interacts with local residing cells to guide their behaviors. The effect of ECM elasticity on cell behaviors has been extensively investigated, while less attention has been paid to the effect of matrix fiber-network plasticity at microscale, although plastic remodeling of fibrous matrix is a common phenomenon in fibrosis. Here, a significant decrease is found in plasticity of native fibrotic tissues, which is associated with an increase in matrix crosslinking. To explore the role of plasticity in fibrosis development, a set of 3D collagen nanofibrous matrix with constant modulus but tunable plasticity is constructed by adjusting the crosslinking degree. Using plasticity-controlled 3D culture models, it is demonstrated that the decrease of matrix plasticity promotes fibroblast activation and spreading. Further, a coarse-grained molecular dynamic model is developed to simulate the cell-matrix interaction at microscale. Combining with molecular experiments, it is revealed that the enhanced fibroblast activation is mediated through cytoskeletal tension and nuclear translocation of Yes-associated protein. Taken together, the results clarify the effects of crosslinking-induced plasticity changes of nanofibrous matrix on the development of fibrotic diseases and highlight plasticity as an important mechanical cue in understanding cell-matrix interactions.


Assuntos
Nanofibras , Colágeno , Matriz Extracelular/patologia , Fibroblastos , Fibrose , Humanos
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