Collective effects in cellular structure formation mediated by compliant environments: A Monte Carlo study

Bischofs, Ilka B.; Schwarz, Ulrich S.

doi:10.1016/j.actbio.2006.01.002

Cited by 24 publications

(21 citation statements)

References 55 publications

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“…[39]. Treatment with lysophosphatidic acid (LPA) can stimulate Rho-mediated contractility [40,26], while treating cells with blebbistatin or cytochalasin D inhibits contractility [34]. At the multicellular level, with increasing uniaxial stretch, our model system switches gradually between networks and strings ( Figure 5).…”

Section: Discussionmentioning

confidence: 99%

Cell Contractility Facilitates Alignment of Cells and Tissues to Static Uniaxial Stretch

Rens

Merks

2017

Biophysical Journal

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During animal development and homeostasis, the structure of tissues, including muscles, blood vessels, and connective tissues, adapts to mechanical strains in the extracellular matrix (ECM). These strains originate from the differential growth of tissues or forces due to muscle contraction or gravity. Here we show using a computational model that by amplifying local strain cues, active cell contractility can facilitate and accelerate the reorientation of single cells to static strains. At the collective cell level, the model simulations show that active cell contractility can facilitate the formation of strings along the orientation of stretch. The computational model is based on a hybrid cellular Potts and finite-element simulation framework describing a mechanical cell-substrate feedback, where: 1) cells apply forces on the ECM, such that 2) local strains are generated in the ECM and 3) cells preferentially extend protrusions along the strain orientation. In accordance with experimental observations, simulated cells align and form stringlike structures parallel to static uniaxial stretch. Our model simulations predict that the magnitude of the uniaxial stretch and the strength of the contractile forces regulate a gradual transition between stringlike patterns and vascular networklike patterns. Our simulations also suggest that at high population densities, less cell cohesion promotes string formation.

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Section: Discussionmentioning

confidence: 99%

Cell Contractility Facilitates Alignment of Cells and Tissues to Static Uniaxial Stretch

Rens

Merks

2017

Biophysical Journal

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“…Closed form expression for the interaction energy between cells can therefore be obtained from Eq (1) by assuming simple models for the distribution of traction applied by each cell. For example, treating cells as force dipoles allows one to predict the most favorable orientation between a pair [19] or a group of cells [20, 21].…”

Section: Methodsmentioning

confidence: 99%

Substrate mediated interaction between pairs of keratocytes: Multipole traction force models describe their migratory behavior

Palmieri

Scanlon²,

Worroll³

et al. 2019

PLoS ONE

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A series of traction force microscopy experiments involving pairs of keratocytes migrating on compliant substrates were analyzed. We observed several instances where keratocytes that are about to collide turn before they touch. We term this phenomenon collision avoidance behavior and we propose that the turning is caused by the substrate mediated elastic interactions between the cells. A multipole analysis of the cell traction reveals that the left-right symmetry of the keratocyte traction pattern is broken during collision avoidance events. The analysis further shows that the cell migration direction reorients before the principal traction dipoles as the cells turn. Linear elasticity theory is used to derive the cell-cell interaction energy between pairs of keratocytes. The traction force applied by each cell is modeled as a two points (dipole) or three points (tripod) force model. We show that both models predict that cells that are about to collide in a head-on manner will turn before touching. The tripod model is further able to account for the quadrupole components of the traction force profile that we observed experimentally. Also, the tripod model proposes a mechanism that may explain why cells tend to scatter with a finite angle after a collision avoidance event. A relationship between the scattering angle and the traction force quadrupole moment is also established. Dynamical simulations of migrating model cells are further used to explain the emergence of other cell pair trajectories that we observed experimentally.

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“…In that vein, several groups have incorporated modeling of peptide presentation by synthetic matrices such as RGD-modified polymer hydrogels to analyze cell adhesion, migration, proliferation and differentiation in terms of the nano-scale distance between adhesion ligands [107][108][109]. Others have used modeling to predict the effects of matrix compliance on cellular organization in the context of tissue formation [110]. In both cases, predictions of bond affinity, structure and intracellular stress sensing are linked to experimentally observed downstream response, rather than initial adhesion.…”

Section: Using Quantitative Measurements Of Cell-materials Interactionmentioning

confidence: 98%

Fluorescent resonance energy transfer: A tool for probing molecular cell–biomaterial interactions in three dimensions

Huebsch

Mooney

2007

Biomaterials

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The current paradigm in designing biomaterials is to optimize material chemical and physical parameters based on correlations between these parameters and downstream biological responses, whether in vitro or in vivo. Extensive developments in molecular design of biomaterials have facilitated identification of several biophysical and biochemical variables (e.g. adhesion peptide density, substrate elastic modulus) as being critical to cell response. However, these empirical observations do not indicate whether different parameters elicit cell responses by modulating redundant variables of the cell-material interface (e.g. number of cell-material bonds, cell-matrix mechanics). Recently, fluorescence resonance energy transfer (FRET) has been applied to quantitatively analyze parameters of the cell-material interface for both two- and three-dimensional adhesion substrates. Tools based on FRET have been utilized to quantify several parameters of the cell-material interface relevant to cell response, including molecular changes in matrix proteins induced by interactions both with surfaces and cells, the number of bonds between integrins and their adhesion ligands, and changes in the crosslink density of hydrogel synthetic extracellular matrix analogs. As such techniques allow both dynamic and 3-D analyses they will be useful to quantitatively relate downstream cellular responses (e.g. gene expression) to the composition of this interface. Such understanding will allow bioengineers to fully exploit the potential of biomaterials engineered on the molecular scale, by optimizing material chemical and physical properties to a measurable set of interfacial parameters known to elicit a predictable response in a specific cell population. This will facilitate the rational design of complex, multi-functional biomaterials used as model systems for studying diseases or for clinical applications.

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Collective effects in cellular structure formation mediated by compliant environments: A Monte Carlo study

Cited by 24 publications

References 55 publications

Cell Contractility Facilitates Alignment of Cells and Tissues to Static Uniaxial Stretch

Cell Contractility Facilitates Alignment of Cells and Tissues to Static Uniaxial Stretch

Substrate mediated interaction between pairs of keratocytes: Multipole traction force models describe their migratory behavior

Fluorescent resonance energy transfer: A tool for probing molecular cell–biomaterial interactions in three dimensions

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