AN ANISOTROPIC BIPHASIC THEORY OF TISSUE-EQUIVALENT MECHANICS - THE INTERPLAY AMONG CELL TRACTION, FIBRILLAR NETWORK DEFORMATION, FIBRIL ALIGNMENT, AND CELL CONTACT GUIDANCE

We present a general mathematical theory for the mechanical interplay in tissue-equivalents (cell-populated collagen gels): Cell traction le ads to compaction of the fibrillar collagen network, which for certain conditions such as a mechanical constraint or inhomogeneous cell dist ribution, can result in inhomogeneous compaction and consequently fibr il alignment, leading to cell contact guidance, which affects the subs equent compaction. The theory accounts for the intrinsically biphasic nature of collagen gel, which is comprised of collagen network and int erstitial solution. The theory also accounts for fibril alignment due to inhomogeneous network deformation that is, anisotropic strain, and for cell alignment in response to fibril alignment. Cell alignment res ults in anisotropic migration and traction, as modeled by a cell orien tation tensor that is a function of a fiber orientation tensor, which is defined by the network deformation tenser. Models for a variety of tissue-equivalents are shown to predict qualitatively the alignment th at arises due to inhomogeneous compaction driven by cell traction.