Modeling and simulation of chemomechanics at the cell-matrix interface

Krishnan, Ranjani; Oommen, Binu; Walton, Emily B.; Maloney, John M.; Vliet, Krystyn J. Van

doi:10.4161/cam.2.2.6154

Cited by 11 publications

(11 citation statements)

References 85 publications

(121 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our finite element study of cell-matrix interactions used geometries of the collagen fibers and cells based on their in vitro morphologies. Several previous finite element studies of mechanical interactions between cells and substrates used homogeneous substrates and idealized cell geometries (45,46). While there is at least one report where images of collagen fibers were used as the basis of computational simulations of the deformation of cell-free collagen gels to externally applied loads (47), we believe that we are the first to use image-based models to understand cell-matrix interactions.…”

Section: Discussionmentioning

confidence: 95%

Fibers in the Extracellular Matrix Enable Long-Range Stress Transmission between Cells

Schickel

Stevenson

et al. 2013

Biophysical Journal

183

201

View full text Add to dashboard Cite

Cells can sense, signal, and organize via mechanical forces. The ability of cells to mechanically sense and respond to the presence of other cells over relatively long distances (e.g., ∼100 μm, or ∼10 cell-diameters) across extracellular matrix (ECM) has been attributed to the strain-hardening behavior of the ECM. In this study, we explore an alternative hypothesis: the fibrous nature of the ECM makes long-range stress transmission possible and provides an important mechanism for long-range cell-cell mechanical signaling. To test this hypothesis, confocal reflectance microscopy was used to develop image-based finite-element models of stress transmission within fibroblast-seeded collagen gels. Models that account for the gel's fibrous nature were compared with homogenous linear-elastic and strain-hardening models to investigate the mechanisms of stress propagation. Experimentally, cells were observed to compact the collagen gel and align collagen fibers between neighboring cells within 24 h. Finite-element analysis revealed that stresses generated by a centripetally contracting cell boundary are concentrated in the relatively stiff ECM fibers and are propagated farther in a fibrous matrix as compared to homogeneous linear elastic or strain-hardening materials. These results support the hypothesis that ECM fibers, especially aligned ones, play an important role in long-range stress transmission.

show abstract

Section: Discussionmentioning

confidence: 95%

Fibers in the Extracellular Matrix Enable Long-Range Stress Transmission between Cells

Schickel

Stevenson

et al. 2013

Biophysical Journal

183

201

View full text Add to dashboard Cite

show abstract

“…Current analytical and computational models of cells on gels (including our nonlinear continuum model) predict a decrease in surface displacement with thickness for a given surface traction (7,9,22). The most pronounced changes are predicted on substrates <5 mm thick regardless of substrate stiffness (28), which is consistent with an increase in effective stiffness and observed cell area (8)(9)(10). These models do not predict the more gradual change in cell area in the 5-to 30-mm thickness range observed on PA gels or the very gradual change in cell area in the 20-150 mm thickness range on protein gels observed in this study.…”

Section: Determining How Far Cells Feel On Biopolymer Gelsmentioning

confidence: 94%

Nonlinear Strain Stiffening Is Not Sufficient to Explain How Far Cells Can Feel on Fibrous Protein Gels

Rudnicki

Cirka

Aghvami

et al. 2013

Biophysical Journal

115

136

View full text Add to dashboard Cite

Recent observations suggest that cells on fibrous extracellular matrix materials sense mechanical signals over much larger distances than they do on linearly elastic synthetic materials. In this work, we systematically investigate the distance fibroblasts can sense a rigid boundary through fibrous gels by quantifying the spread areas of human lung fibroblasts and 3T3 fibroblasts cultured on sloped collagen and fibrin gels. The cell areas gradually decrease as gel thickness increases from 0 to 150 μm, with characteristic sensing distances of >65 μm below fibrin and collagen gels, and spreading affected on gels as thick as 150 μm. These results demonstrate that fibroblasts sense deeper into collagen and fibrin gels than they do into polyacrylamide gels, with the latter exhibiting characteristic sensing distances of <5 μm. We apply finite-element analysis to explore the role of strain stiffening, a characteristic mechanical property of collagen and fibrin that is not observed in polyacrylamide, in facilitating mechanosensing over long distances. Our analysis shows that the effective stiffness of both linear and nonlinear materials sharply increases once the thickness is reduced below 5 μm, with only a slight enhancement in sensitivity to depth for the nonlinear material at very low thickness and high applied traction. Multiscale simulations with a simplified geometry predict changes in fiber alignment deep into the gel and a large increase in effective stiffness with a decrease in substrate thickness that is not predicted by nonlinear elasticity. These results suggest that the observed cell-spreading response to gel thickness is not explained by the nonlinear strain-stiffening behavior of the material alone and is likely due to the fibrous nature of the proteins.

show abstract

“…In fact, it is not currently computational feasible to model an entire focal adhesion complex at the atomistic level [68]. …”

Section: Cell-biomaterials Interaction Modelsmentioning

confidence: 99%

Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives

Sanz-Herrera

Reina-Romo

2011

IJMS

View full text Add to dashboard Cite

Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle) levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields.

show abstract

Modeling and simulation of chemomechanics at the cell-matrix interface

Cited by 11 publications

References 85 publications

Fibers in the Extracellular Matrix Enable Long-Range Stress Transmission between Cells

Fibers in the Extracellular Matrix Enable Long-Range Stress Transmission between Cells

Nonlinear Strain Stiffening Is Not Sufficient to Explain How Far Cells Can Feel on Fibrous Protein Gels

Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives

Contact Info

Product

Resources

About