Probing Local Force Propagation in Tensed Fibrous Gels

Abstract

Fibrous hydrogels are a key component of soft animal tissues. They support cellular functions and facilitate efficient mechanical communication between cells. Due to their nonlinear mechanical properties, fibrous materials display non‐trivial force propagation at the microscale, that is enhanced compared to that of linear‐elastic materials. In the body, tissues are constantly subjected to external loads that tense or compress them, modifying their micro‐mechanical properties into an anisotropic state. However, it is unknown how force propagation is modified by this isotropic‐to‐anisotropic transition. Here, force propagation in tensed fibrin hydrogels is directly measured. Local perturbations are induced by oscillating microspheres using optical tweezers. 1‐point and 2‐point microrheology are combined to simultaneously measure the shear modulus and force propagation. A mathematical framework to quantify anisotropic force propagation trends is suggested. Results show that force propagation becomes anisotropic in tensed gels, with, surprisingly, stronger response to perturbations perpendicular to the axis of tension. Importantly, external tension can also increase the range of force transmission. Possible implications and future directions for research are discussed. These results suggest a mechanism for favored directions of mechanical communication between cells in a tissue under external loads.

Anomalous linear elasticity of disordered networks

“…Recent experiments on tensed fibrin hydrogels [19] show that the linear response [33] to a point force is anomalous, decaying as 1/r β away from the perturbation -with β measurably smaller than 1 -, instead of the 1/r decay expected from continuum linear elasticity. These results indicate that the mechanism generating anomalous elastic responses might not be the intrinsic nonlinearity of the constituent elements, as invoked in several previous works [14][15][16][17][18], but rather the physics discussed here.…”

“…[14][15][16][17][18] Contrary to those studies, in this work we consider model systems in which an anomalous linear response emerges, as also recently shown to occur in experiments on tensed fibrous hydrogels. 19 We finally note that other approaches termed 'anomalous elasticity'-describing different mechanical phenomena in amorphous materials-were recently put forward. [20][21][22]…”

Micropatterning the organization of multicellular structures in 3D biological hydrogels; insights into collective cellular mechanical interactions

“…Cells respond to the deformed bands by aligning their stress fibers and integrins in the direction of the gel fibers, and this process is forcedependent as revealed by treatment with blebbistatin. The increased stiffness, anisotropy and alignment associated with remodeled band regions can impact cell morphology and directional migration [56][57][58]. In parallel, the 2D glass control experiment provides further evidence that the directed cell migration along bands is not driven by biochemical signaling.…”

“…Cell migration on the glass was more random without a clear preference to neighboring clusters, unlike the situation in the gel, suggesting that the involvement of biochemical signals in directing cell movement is less prominent. These results collectively suggest that cell migration directionality is driven by cues presented by the deformed band regions, such as the increased local stiffness, anisotropy or topology of the aligned fibers [56][57][58].…”

Local response and emerging nonlinear elastic length scale in biopolymer matrices

“…Living tissues are naturally nonlinear materials, and it is known that cells can trigger the nonlinear stiffening of their matrices and induce long-ranged mechanical fields ( 8 , 43 , 44 ). Unlike on linear elastic substrates, the matrix nonlinearity complicates cell–cell interaction and collective cell behaviors within these matrices.…”