Biology subjects

Moriel, A.

Publications and source records attributed to Moriel, A..

3 recordsLinked to original sources

bioRxiv2022

Characteristic energy scales of active fluctuations in adherent cells

Cell-matrix and cell-cell adhesion play important roles in a wide variety of physiological processes, from the single cell level to the large scale, multicellular organization of tissues. Cells actively apply forces to their environment, either extracellular matrix or neighboring cells, as well as sense its biophysical properties. The fluctuations associated with these active processes occur on an energy scale much larger than that of ordinary thermal equilibrium fluctuations, yet their statistical properties and characteristic scales are not fully understood. Here, we compare measurements of the energy scale of active cellular fluctuations -- an effective cellular temperature -- in four different biophysical settings, involving both single cell and cell aggregates experiments under various control conditions, different cell types and various biophysical observables. The results indicate that a similar energy scale of active fluctuations might characterize the same cell type in different settings, though it may vary among different cell types, being approximately 6 to 8 order of magnitude larger than the ordinary thermal energy at room temperature. These findings call for extracting the energy scale of active fluctuations over a broader range of cell types, experimental settings and biophysical observables, and for understanding the biophysical origin and significance of such cellular energy scales.

biophysics↗

bioRxiv2022

Cellular orientational fluctuations, rotational diffusion and nematic order under periodic driving

The ability of living cells to sense the physical properties of their microenvironment and to respond to dynamic forces acting on them plays a central role in regulating their structure, function and fate. Of particular importance is the cellular sensitivity and response to periodic driving forces in noisy environments, encountered in vital physiological conditions such as heart beating, blood vessels pulsation and breathing. Here, we first test and validate two predictions of a mean-field theory of cellular reorientation under periodic driving, which combines the minimization of cellular anisotropic elastic energy with active remodeling forces. We then extend the mean-field theory to include uncorrelated, additive nonequilibrium fluctuations, and show that the theory quantitatively agrees with the experimentally observed stationary probability distributions of the cell body orientation, under a range of biaxial periodic driving forces. The fluctuations theory allows to extract the dimensionless active noise amplitude of various cell types, and consequently their rotational diffusion coefficient. We then focus on intra-cellular nematic order, i.e. on orientational fluctuations of actin stress fibers around the cell body orientation, and show experimentally that intra-cellular nematic order increases with both the magnitude of the driving forces and the biaxiality strain ratio. These results are semi-quantitatively explained by applying the same cell body fluctuations theory to orientationally correlated actin stress fiber domains. The implications of these findings, which make the quantitative analysis of cell mechanosensitivity more accessible, are discussed.

cell biology↗

bioRxiv2020

Epithelial Tissues as Active Solids: From Nonlinear Contraction Pulses to Rupture Resistance

Epithelial tissues in many contexts can be viewed as soft active solids. Their active nature is manifested in the ability of individual cells within the tissue to contract and/or remodel their mechanical properties in response to various conditions. Little is known about the emergent properties of such materials. Specifically, how an individual cellular activity gives rise to collective spatiotemporal patterns is not fully understood. Recently we reported the observation of ultrafast contraction pulses in the dorsal epithelium of T.adhaerens in vivo [1] and speculated these propagate via mechanical fields. Other accumulating evidence suggest mechanics is involved in similar contractile patterns in embryonic development in vivo and in cellular monolayers in vitro. Here we show that a widespread cellular response - activation of contraction in response to stretch - is sufficient to give rise to nonlinear propagating contraction pulses. Using a minimal numerical model and theoretical considerations we show how such mechanical pulses emerge and propagate, spontaneously or in response to external stretch. The model - whose mathematical structure resembles that of reaction-diffusion systems - explains observed phenomena in T. adhaerens (e.g. excitable or spontaneous pulses, pulse interaction) and predicts other phenomena (e.g. symmetric strain profile, "spike trains"). Finally, we show that in response to external tension, such an active two-dimensional sheet lowers and dynamically distributes the strains across its surface, hence facilitating tissue resistance to rupture. Adding a cellular softening-threshold further enhances the tissue resistance to rupture at cell-cell junctions. As cohesion is at the heart of epithelial physiology, our model may be relevant to many other epithelial systems, even if manifested at different time/length scales. SignificanceOur work demonstrates that many observed dynamical phenomena in epithelial tissues can be explained merely by mechanical cell-cell interactions, and do not require chemical diffusion or transport between cells (though chemical activity may participate in relevant intracellular processes). Specifically, we show that single cell extension-induced-contraction (EIC) is sufficient to generate propagating contraction pulses, which also increase the tissues resistance to rupture, an essential function of epithelia. Our results may shed light on how epithelial tissues function under challenging physiological conditions, e.g. in lung, gut, vasculature and other biomedical contexts. Our results may also be relevant in the study of early evolution of multicellularity and the nervous-muscular systems. Finally, the work offers guidelines for designing soft synthetic solids with improved mechanical properties.

biophysics↗