Abstract
Cells contracting in extracellular matrix (ECM) can transmit stress over long distances, communicating their position and orientation to cells many tens of micrometres away. Such phenomena are not observed when cells are seeded on substrates with linear elastic properties, such as polyacrylamide (PA) gel. The ability for fibrous substrates to support far reaching stress and strain fields has implications for many physiological processes, while the mechanical properties of ECM are central to several pathological processes, including tumour invasion and fibrosis. Theoretical models have investigated the properties of ECM in a variety of network geometries. However, the effects of network architecture on mechanical cell–cell communication have received little attention. This work investigates the effects of geometry on network mechanics, and thus the ability for cells to communicate mechanically through different networks. Cell-derived displacement fields are quantified for various network geometries while controlling for network topology, cross-link density and micromechanical properties. We find that the heterogeneity of response, fibre alignment, and substrate displacement fields are sensitive to network choice. Further, we show that certain geometries support mechanical communication over longer distances than others. As such, we predict that the choice of network geometry is important in fundamental modelling of cell–cell interactions in fibrous substrates, as well as in experimental settings, where mechanical signalling at the cellular scale plays an important role. This work thus informs the construction of theoretical models for substrate mechanics and experimental explorations of mechanical cell–cell communication.
Highlights
How cells interact with their substrate is of fundamental importance to many physiological processes, ranging from cell communication (Reinhart-King et al 2008; Winer et al 2009), motility and migration (Lo et al 2000), cell fate (Engler et al 2006; Gilbert et al 2010) and morphology (Yeung et al 2005)
We further investigate whether constituent fibre strain distributions are affected by geometry choice, and the plausibility of mechanical cell–cell communication within networks of different architectures
We have presented a whole network model for fibrous substrates which employed four different geometries
Summary
How cells interact with their substrate is of fundamental importance to many physiological processes, ranging from cell communication (Reinhart-King et al 2008; Winer et al 2009), motility and migration (Lo et al 2000), cell fate (Engler et al 2006; Gilbert et al 2010) and morphology (Yeung et al 2005). A clear understanding of this microenvironment is challenging, in part due to the non-affine response of the substrate (Wilhelm and Frey 2003; Chandran and Barocas 2006). Further complexity is introduced in cell-matrix interactions, which occur in a feedback loop termed ‘dynamic reciprocity’. Substrate reorganises under cell-generated tractions, leading to a strain-stiffening response which feeds back into an intracellular response. Realignment of network fibres under traction leads to fibre bundling along the load direction, contributing to a stiffer mechanical response. Actomyosin bundles important for cell contraction, are subsequently recruited to sites of high stiffness, leading to further cell contraction, whence the feedback loop continues (Discher et al 2005). Investigating how matrix alignment and stiffness are related is important for developing a better understanding of cell-matrix interactions
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