Strain-Induced Alignment in Collagen Gels

Abstract

Collagen is the most abundant extracellular-network-forming protein in animal biology and is important in both natural and artificial tissues, where it serves as a material of great mechanical versatility. This versatility arises from its almost unique ability to remodel under applied loads into anisotropic and inhomogeneous structures. To explore the origins of this property, we develop a set of analysis tools and a novel experimental setup that probes the mechanical response of fibrous networks in a geometry that mimics a typical deformation profile imposed by cells in vivo. We observe strong fiber alignment and densification as a function of applied strain for both uncrosslinked and crosslinked collagenous networks. This alignment is found to be irreversibly imprinted in uncrosslinked collagen networks, suggesting a simple mechanism for tissue organization at the microscale. However, crosslinked networks display similar fiber alignment and the same geometrical properties as uncrosslinked gels, but with full reversibility. Plasticity is therefore not required to align fibers. On the contrary, our data show that this effect is part of the fundamental non-linear properties of fibrous biological networks.

Rapid disorganization of mechanically interacting systems of mammary acini

“…1 C and D and Movie S1). As expected based on the previous literature (8,10), the acini concentrated the collagen around and among them (Movies S2-S6), yielding pairs and clusters of acini interconnected by lines of intense collagen signal. By about 10 h, some of the acini began to disorganize, and by 20 h, many acini had lost their regular, spherical morphology, and single cells were leaving the acini and scattering on the collagen.…”

“…In certain situations, contractile multicellular structures are able to mechanically reorganize biopolymer networks over long distances and in a highly directional manner, generating what are variously referred to as fibers, tracts, cables, straps, or lines. Regions of highly directional collagen alignment and concentration have been seen in systems ranging from single cells and tumor explants to human clinical samples (6,8,10,(20)(21)(22). Vader et al demonstrated that the formation of long collagen lines is a mechanical phenomenon that reflects the fundamental nonlinear properties of fibrous biological networks (10).…”

“…The ECM confers mechanical integrity to tissues and provides chemical, anatomical, and mechanical signals to cells, influencing differentiation, development, and pathogenesis (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). The extent to which mechanical cues are generated and received by individual cells has been studied both experimentally and theoretically (12)(13)(14).…”

“…Regions of highly directional collagen alignment and concentration have been seen in systems ranging from single cells and tumor explants to human clinical samples (6,8,10,(20)(21)(22). Vader et al demonstrated that the formation of long collagen lines is a mechanical phenomenon that reflects the fundamental nonlinear properties of fibrous biological networks (10). Collagen lines control the morphogenesis of epithelial tubular patterns (8) and may also influence where and when tumors invade the surrounding stroma.…”

An investigation of the influence of extracellular matrix anisotropy and cell–matrix interactions on tissue architecture

“…The mechanics of textile fibres (felt, or tufts of fibres, undergoing elongation or the carding process) have been studied, both experimentally and theoretically by Kabla and Mahadevan (2007); Lee and Ockendon (2005). Similar experimental (Vader et al, 2009), and theoretical (Green and Friedman, 2008), studies of collagen gels have also been undertaken. In biological contexts, however, the focus is frequently on how properties such as fibre alignment or ECM deformation affect cell behaviour.…”