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1.
J R Soc Interface ; 19(190): 20220102, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35506211

RESUMO

Insect load sensors, called campaniform sensilla (CS), measure strain changes within the cuticle of appendages. This mechanotransduction provides the neuromuscular system with feedback for posture and locomotion. Owing to their diverse morphology and arrangement, CS can encode different strain directions. We used nano-computed tomography and finite-element analysis to investigate how different CS morphologies within one location-the femoral CS field of the leg in the fruit fly Drosophila-interact under load. By investigating the influence of CS substructures' material properties during simulated limb displacement with naturalistic forces, we could show that CS substructures (i.e. socket and collar) influence strain distribution throughout the whole CS field. Altered socket and collar elastic moduli resulted in 5% relative differences in displacement, and the artificial removal of all sockets caused differences greater than 20% in cap displacement. Apparently, CS sockets support the distribution of distal strain to more proximal CS, while collars alter CS displacement more locally. Harder sockets can increase or decrease CS displacement depending on sensor location. Furthermore, high-resolution imaging revealed that sockets are interconnected in subcuticular rows. In summary, the sensitivity of individual CS is dependent on the configuration of other CS and their substructures.


Assuntos
Insetos , Mecanotransdução Celular , Animais , Fenômenos Biomecânicos , Biofísica , Insetos/fisiologia , Sensilas
2.
Nature ; 605(7908): 37-38, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35508770
3.
Methods Mol Biol ; 2502: 329-349, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35412249

RESUMO

Cancer metastasis, that is, the spreading of tumor cells from the primary tumor to distant sites, requires cancer cells to travel through pores substantially smaller than their cross section . This "confined migration" requires substantial deformation by the relatively large and rigid nucleus, which can impact nuclear compartmentalization, trigger cellular mechanotransduction pathways, and increase genomic instability. To improve our understanding of how cells perform and respond to confined migration, we developed polydimethylsiloxane (PDMS) microfluidic devices in which cells migrate through a precisely controlled "field of pillars" that closely mimic the intermittent confinement of tumor microenvironments and interstitial spaces. The devices can be designed with various densities of pillars, ranging from a very low density that does not require nuclear deformation to high densities that present microenvironment conditions with severe confinement. The devices enable assessment of cellular fitness for confined migration based on the distance traveled through the constriction area over several days. In this protocol, we present two complementary techniques to generate silicon master molds for the device fabrication: (1) SU-8 soft lithography for rapid prototyping and for devices with relatively large features; and (2) reactive ion etching (RIE) to achieve finer features and more durable molds. In addition, we describe the production, use, and validation of the devices, along with the analysis pipeline for experiments using the devices with fluorescently labeled cells. Collectively, this protocol enables the study of confined migration and is readily amendable to investigate other aspects of confined migration mechanobiology, such as nuclear pore complex function in response to nuclear deformation.


Assuntos
Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Biofísica , Movimento Celular/fisiologia , Núcleo Celular , Mecanotransdução Celular
4.
Biofabrication ; 14(3)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35378520

RESUMO

Tissue biomanufacturing aims to produce lab-grown stem cell grafts and biomimetic drug testing platforms but remains limited in its ability to recapitulate native tissue mechanics. The emerging field of soft robotics aims to emulate dynamic physiological locomotion, representing an ideal approach to recapitulate physiologically complex mechanical stimuli and enhance patient-specific tissue maturation. The kneecap's femoropopliteal artery (FPA) represents a highly flexible tissue across multiple axes during blood flow, walking, standing, and crouching positions, and these complex biomechanics are implicated in the FPA's frequent presentation of peripheral artery disease. We developed a soft pneumatically actuated (SPA) cell culture platform to investigate how patient-specific FPA mechanics affect lab-grown arterial tissues. Silicone hyperelastomers were screened for flexibility and biocompatibility, then additively manufactured into SPAs using a simulation-based design workflow to mimic normal and diseased FPA extensions in radial, angular, and longitudinal dimensions. SPA culture platforms were seeded with mesenchymal stem cells, connected to a pneumatic controller, and provided with 24 h multi-axial exercise schedules to demonstrate the effect of dynamic conditioning on cell alignment, collagen production, and muscle differentiation without additional growth factors. Soft robotic bioreactors are promising platforms for recapitulating patient-, disease-, and lifestyle-specific mechanobiology for understanding disease, treatment simulations, and lab-grown tissue grafts.


Assuntos
Robótica , Artérias , Fenômenos Biomecânicos , Biofísica , Humanos
5.
J R Soc Interface ; 19(189): 20210880, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35440204

RESUMO

The cell nucleus plays a critical role in mechanosensing and mechanotransduction processes, by adaptive changes of its envelope composition to external biophysical stimuli such as substrate rigidity and tensile forces. Current measurement approaches lack precise control in stress application on nuclei, thus significantly impairing a complete mechanobiological study of cells. Here, we present a contactless microfluidic approach capable to exert a wide range of viscoelastic compression forces (10-103 µN)-as an alternative to adhesion-related techniques-to induce cell-specific mechano-structural and biomolecular changes. We succeed in monitoring substantial nuclear modifications in Lamin A/C expression and coverage, diffusion processes of probing molecules, YAP shuttling, chromatin re-organization and cGAS pathway activation. As a result, high compression forces lead to a nuclear reinforcement (e.g. up to +20% in Lamin A/C coverage) or deconstruction (e.g. down to -45% in Lamin A/C coverage with a 30% reduction of chromatin condensation state parameter) up to cell death. We demonstrate how wide-range compression on suspended cells can be used as a tool to investigate nuclear mechanobiology and to define specific nuclear signatures for cell mechanical phenotyping.


Assuntos
Lamina Tipo A , Microfluídica , Biofísica , Núcleo Celular/metabolismo , Cromatina/metabolismo , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Mecanotransdução Celular/fisiologia
7.
Methods Mol Biol ; 2502: 299-310, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35412247

RESUMO

Atomic force microscopy (AFM) enables simultaneous generation of topographical and biophysical maps of surfaces of biological samples at nanoresolution in physiologically relevant environments. Here, we describe the application of AFM to study nuclear pore complexes from structural and biophysical aspects.


Assuntos
Poro Nuclear , Biofísica , Microscopia de Força Atômica
8.
PLoS One ; 17(4): e0265934, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35390020

RESUMO

Changes in gray whale (Eschrichtius robustus) phenology and distribution are related to observed and hypothesized prey availability, bottom water temperature, salinity, sea ice persistence, integrated water column and sediment chlorophyll a, and patterns of wind-driven biophysical forcing in the northern Bering and eastern Chukchi seas. This portion of the Pacific Arctic includes four Distributed Biological Observatory (DBO) sampling regions. In the Bering Strait area, passive acoustic data showed marked declines in gray whale calling activity coincident with unprecedented wintertime sea ice loss there in 2017-2019, although some whales were seen there during DBO cruises in those years. In the northern Bering Sea, sightings during DBO cruises show changes in gray whale distribution coincident with a shrinking field of infaunal amphipods, with a significant decrease in prey abundance (r = -0.314, p<0.05) observed in the DBO 2 region over the 2010-2019 period. In the eastern Chukchi Sea, sightings during broad scale aerial surveys show that gray whale distribution is associated with localized areas of high infaunal crustacean abundance. Although infaunal crustacean prey abundance was unchanged in DBO regions 3, 4 and 5, a mid-decade shift in gray whale distribution corresponded to both: (i) a localized increase in infaunal prey abundance in DBO regions 4 and 5, and (ii) a correlation of whale relative abundance with wind patterns that can influence epi-benthic and pelagic prey availability. Specifically, in the northeastern Chukchi Sea, increased sighting rates (whales/km) associated with an ~110 km (60 nm) offshore shift in distribution was positively correlated with large scale and local wind patterns conducive to increased availability of krill. In the southern Chukchi Sea, gray whale distribution clustered in all years near an amphipod-krill 'hotspot' associated with a 50-60m deep trough. We discuss potential impacts of observed and inferred prey shifts on gray whale nutrition in the context of an ongoing unusual gray whale mortality event. To conclude, we use the conceptual Arctic Marine Pulses (AMP) model to frame hypotheses that may guide future research on whales in the Pacific Arctic marine ecosystem.


Assuntos
Euphausiacea , Baleias , Animais , Regiões Árticas , Biofísica , Clorofila A , Ecossistema , Oceanos e Mares , Água
9.
Molecules ; 27(7)2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35408504

RESUMO

Molecular dynamics (MD) simulations have led to great advances in many scientific disciplines, such as chemical physics, materials science, and biophysics [...].


Assuntos
Simulação de Dinâmica Molecular , Biofísica
10.
Nature ; 604(7904): 46-47, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379991
11.
Adv Exp Med Biol ; 1359: 25-67, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35471534

RESUMO

The first step toward understanding the brain is to learn how individual neurons process incoming signals, the vast majority of which arrive in their dendrites. Dendrites were first discovered at the beginning of the twentieth century and were characterized by great anatomical variability, both within and across species. Over the past years, a rich repertoire of active and passive dendritic mechanisms has been unveiled, which greatly influences their integrative power. Yet, our understanding of how dendrites compute remains limited, mainly because technological limitations make it difficult to record from dendrites directly and manipulate them. Computational modeling, on the other hand, is perfectly suited for this task. Biophysical models that account for the morphology as well as passive and active neuronal properties can explain a wide variety of experimental findings, shedding new light on how dendrites contribute to neuronal and circuit computations. This chapter aims to help the interested reader build biophysical models incorporating dendrites by detailing how their electrophysiological properties can be described using simple mathematical frameworks. We start by discussing the passive properties of dendrites and then give an overview of how active conductances can be incorporated, leading to realistic in silico replicas of biological neurons.


Assuntos
Dendritos , Neurônios , Biofísica , Simulação por Computador , Dendritos/fisiologia , Neurônios/fisiologia , Sinapses/fisiologia
12.
J Biomech ; 136: 111084, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35428000

RESUMO

The mechanisms by which cells respond to their changing mechanical environment and how this stimulus is decoded intracellularly from the tissue to the organ level, are widely considered as fundamental for most biological processes. Despite this, the underlying phenomena of mechanotransduction, are still not very well understood. Over the last years, numerical modeling has emerged as a cohesive element in the interpretation of biophysical and biochemical assays, concerning cellular mechanotransduction. We hypothesize that the consideration of continuum mechanics (studying all cellular entities as solids) is an inherent limitation of these models, and in part, responsible for their restricted application in cellular biomechanics. To evaluate this, a (verified and validated) 3D model of osteoblast is simulated through structural analysis, employing conventional Finite Element (FE) modelling and the results compared to a Fluid-Structure Interaction (FSI) analysis. Among the trend observed, FSI systematically leads to a higher stimulation of the nucleus (by up to 200%), while FE produced a more uniform stress field, resulting in the deformation of a notably larger portion of its volume. Although FE modelling captures a seemingly correct kinematic response of the cell when subjected to the simulated loading scenario, FSI represents a more realistic alternative. The equitable consideration of both, liquid- and solid-state material characteristics, in the latter analysis, revealed intra-cellular loading patterns that were more realistic from a biomechanical perspective. In conclusion, FSI can provide refined insight as to nuclear loading, thus serving as a far more accurate framework for decoding cellular mechanotransduction.


Assuntos
Mecanotransdução Celular , Fenômenos Biomecânicos , Biofísica , Simulação por Computador , Análise de Elementos Finitos , Estresse Mecânico
13.
J R Soc Interface ; 19(189): 20210943, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35414213

RESUMO

Proven as a natural barrier against viral infection, pulmonary surfactant phospholipids have a biophysical and immunological role within the respiratory system, acting against microorganisms including viruses. Enveloped viruses have, in common, an outer bilayer membrane that forms the underlying structure for viral membrane proteins to function in an optimal way to ensure infectivity. Perturbating the membrane of viruses using exogenous lipids can be envisioned as a generic way to reduce their infectivity. In this context, the potential of exogenous lipids to be used against enveloped virus infectivity would be indicated by the resulting physical stress imposed to the viral membrane, and conical lipids, i.e. lyso-lipids, would be expected to generate stronger biophysical disturbances. We confirm that when treated with lyso-lipids the infectivity three strains of influenza virus (avian H2N3, equine H3N8 or pandemic human influenza H1N1) is reduced by up to 99% in a cell-based model. By contrast, lipids with a similar head group but two aliphatic chains were less effective (reducing infection by only 40-50%). This work opens a new path to merge concepts from different research fields, i.e. 'soft matter physics' and virology.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N8 , Influenza Humana , Animais , Biofísica , Cavalos , Humanos , Lipídeos
14.
Eur Biophys J ; 51(2): 97-98, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35316358
15.
Biophys J ; 121(8): 1435-1448, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35300969

RESUMO

The patch-clamp method, which was awarded the Nobel Prize in 1991, is a well-established and indispensable method to study ion channels in living cells and to biophysically characterize non-voltage-gated ion channels, which comprise about 70% of all ion channels in the human genome. To investigate the biophysical properties of non-voltage-gated ion channels, whole-cell measurements with application of continuous voltage ramps are routinely conducted to obtain current-voltage (IV) relationships. However, adequate tools for detailed and quantitative analysis of IV curves are still missing. We use the example of the transient receptor potential classical (TRPC) channel family to elucidate whether the normalized slope conductance (NSC) is an appropriate tool for reliable discrimination of the IV curves of diverse TRPC channels that differ in their individual curve progression. We provide a robust calculation method for the NSC, and, by applying this method, we find that TRPC channel activators and modulators can evoke different NSC progressions independent from their expression levels, which points to distinguishable active channel states. TRPC6 mutations in patients with focal segmental glomerulosclerosis resulted in distinct NSC progressions, suggesting that the NSC is suitable for investigating structure-function relations and might help unravel the unknown pathomechanisms leading to focal segmental glomerulosclerosis. The NSC is an effective algorithm for extended biophysical characterization of non-voltage-gated ion channels.


Assuntos
Glomerulosclerose Segmentar e Focal , Biofísica , Feminino , Humanos , Canais Iônicos , Masculino , Técnicas de Patch-Clamp
16.
J R Soc Interface ; 19(188): 20210955, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35291831

RESUMO

The female locust has a unique mechanism for digging in order to deposit its eggs deep in the ground. It uses two pairs of sclerotized valves to displace the granular matter, while extending its abdomen as it propagates underground. This ensures optimal conditions for the eggs to incubate and provides them with protection from predators. Here, the direction-dependent biomechanics of the locust's major, dorsal digging valves are quantified and analysed under forces in the physiological range and beyond, considering the hydration level as well as the females' sexual maturation state. Our findings reveal that the responses of the valves to compression forces in the digging and propagation directions change upon sexual maturation to follow their function and depend on environmental conditions. In addition, mature females, which lay eggs, have stiffer valves, up to approximately 19 times the stiffness of the pre-mature locusts. The valves are stiffer in the major working direction, corresponding to soil shuffling and compression, compared with the direction of propagation. Hydration of the valves reduces their stiffness but increases their resilience against failure. These findings provide mechanical and materials guidelines for the design of novel non-drilling burrowing tools, including three-dimensionally printed anisotropic materials based on composites.


Assuntos
Gafanhotos , Animais , Fenômenos Biomecânicos , Biofísica , Feminino , Gafanhotos/fisiologia , Oviposição/fisiologia
17.
Sci Rep ; 12(1): 3992, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35273205

RESUMO

Bio-impedance non-invasive measurement techniques usage is rapidly increasing in the agriculture industry. These measured impedance variations reflect tacit biochemical and biophysical changes of living and non-living tissues. Bio-impedance circuit modeling is an effective solution used in biology and medicine to fit the measured impedance. This paper proposes two new fractional-order bio-impedance plant stem models. These new models are compared with three commonly used bio-impedance fractional-order circuit models in plant modeling (Cole, Double Cole, and Fractional-order Double-shell). The two proposed models represent the characterization of the biological cellular morphology of the plant stem. Experiments are conducted on two samples of three different medical plant species from the family Lamiaceae, and each sample is measured at two inter-electrode spacing distances. Bio-impedance measurements are done using an electrochemical station (SP150) in the range of 100 Hz to 100 kHz. All employed models are compared by fitting the measured data to verify the efficiency of the proposed models in modeling the plant stem tissue. The proposed models give the best results in all inter-electrode spacing distances. Four different metaheuristic optimization algorithms are used in the fitting process to extract all models parameter and find the best optimization algorithm in the bio-impedance problems.


Assuntos
Algoritmos , Biofísica , Impedância Elétrica , Eletrodos , Caules de Planta
18.
Biomaterials ; 283: 121427, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35276617

RESUMO

Therapeutic strategies aimed at overcoming the loss of myelin sheath in central nervous system demyelinating diseases are often unsuccessful due to nescience underlying the mechanisms of remyelination failure. The environment surrounding a demyelination lesion is seen as a hostile terrain, characterized by factors that can inhibit myelin production by oligodendrocytes (OLs). The formation of a glial scar containing reactive astrocytes producing high amounts of altered matrix proteins can compromise OL remyelination. Allied to glial scar, mechanical properties of the tissue are altered. The paradigms in the remyelination failure are changing. We point mechanobiology as a missing key towards unravelling the nature of (de)myelination. Mechanical cues as stiffness, axonal tension or physical constraints are emerging as dictators of tissue homeostasis and pathology. Here we delve into an in-depth characterization of the preeminent models to study mechanobiology events of (de)myelination and remyelination. Alternatives to in vivo systems are provided, either through the exploration of simpler animal models, creation of in vitro models using tissue engineered approaches or through in silico tools. We discuss how bioengineering is being explored to generate relevant models to dissect new mechanobiology mechanisms and identify novel therapeutic targets, being expected to profoundly impact the treatment of demyelinating diseases.


Assuntos
Doenças Desmielinizantes , Remielinização , Animais , Bioengenharia , Biofísica , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/patologia , Bainha de Mielina/metabolismo , Oligodendroglia/metabolismo , Remielinização/fisiologia
19.
Colloids Surf B Biointerfaces ; 214: 112429, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35278859

RESUMO

The tear film lipid layer (TFLL) is important to the maintenance of ocular surface health. Surprisingly, information on the individual roles of the myriad of unique lipids found therein is limited. The most abundant lipid species are the wax esters (WE) and cholesteryl esters (CE), and, especially their branched analogs. The isolation of these lipid species from the TFLL has proved to be tedious, and as a result, insights on their biophysical profiles and role in the TFLL is currently lacking. Herein, we circumvent these issues by a total synthesis of the most abundant iso-methyl branched WEs and CEs found in the TFLL. Through a detailed characterization of the biophysical properties, by the use of Langmuir monolayer and wide-angle X-ray scattering techniques, we demonstrate that chain branching alters the behavior of these lipid species on multiple levels. Taken together, our results fill an important knowledge gap concerning the structure and function of the TFLL on the whole.


Assuntos
Ésteres do Colesterol , Lipídeos , Biofísica , Ésteres do Colesterol/química , Ésteres , Lipídeos/química , Lágrimas/química
20.
Comput Biol Med ; 144: 105328, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35231800

RESUMO

Transcranial electrode stimulation (tES), one of the techniques used to apply non-invasive brain stimulation (NIBS), modulates cortical activities by delivering weak electric currents through scalp-attached electrodes. This emerging technique has gained increasing attention recently; however, the results of tES vary greatly depending upon subjects and the stimulation paradigm, and its cellular mechanism remains unclear. In particular, there is a controversy over the factors that determine the cortical response to tES. Some studies have reported that the electric field's (EF) orientation is the determining factor, while others have demonstrated that the EF magnitude itself is the crucial factor. In this work, we conducted an in-depth investigation of cortical activity in two types of electrode montages used widely-the conventional (C)-tES and high-definition (HD)-tES-as well as two stimulation waveforms-direct current (DC) and alternating current (AC). To do so, we constructed a multi-scale model by coupling an anatomically realistic human head model and morphologically realistic multi-compartmental models of three types of cortical neurons (layer 2/3 pyramidal neuron, layer 4 basket cell, layer 5 pyramidal neuron). Then, we quantified the neuronal response to the C-/HD-tDCS/tACS and explored the relation between the electric field (EF) and the radial field's (RF: radial component of EF) magnitude and the cortical neurons' threshold. The EF tES induced depended upon the electrode montage, and the neuronal responses were correlated with the EF rather than the RF's magnitude. The electrode montages and stimulation waveforms caused a small difference in threshold, but the higher correlation between the EF's magnitude and the threshold was consistent. Further, we observed that the neurons' morphological features affected the degree of the correlation highly. Thus, the EF magnitude was a key factor in the responses of neurons with arborized axons. Our results demonstrate that the crucial factor in neuronal excitability depends upon the neuron models' morphological and biophysical properties. Hence, to predict the cellular targets of NIBS precisely, it is necessary to adopt more advanced neuron models that mimic realistic morphological and biophysical features of actual human cells.


Assuntos
Estimulação Transcraniana por Corrente Contínua , Biofísica , Encéfalo/fisiologia , Estimulação Elétrica , Eletricidade , Eletrodos , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos
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