Mechanical Properties of Type I Collagen and Biopolymer Networks for Use as 3D Substrates in Cell Culture
Googins, Kara Forbes
Blair, Daniel L
Extracellular matrix proteins such as collagen self-assemble to form branched networksthat undergo dramatic structural changes in response to shear deformations.Collagen fibers locally transform the applied shear from non-affine to affine throughreorientation and elongation. Under applied shear, the stress response of the networktransitions from a linear relationship with the linear modulus G0 into a non-linearstrain-stiffening regime. I manipulate collagen network connectivity, branching density,and individual fiber mechanics by controlling the polymerization conditions andintroducing additional chemical cross-links post-polymerization. I find that the linearelastic modulus of the network does not predict the onset of nonlinear behavior.In particular, it is the network structure that sets the strain for the onset of thestretch-dominated non-linear regime, as well as the network yield strain. Individualfiber mechanics set the stresses within the network during the stretch-dominatednon-linear regime. Next I investigate the stress relaxation of type-I collagen networksunder a held shear strain. Relaxation is highly dependent on the amount of cross-linkingpresent, suggesting a fiber level mechanism for the reduction of stress heldwithin the network. To form a connection between the bulk rheological and individualfiber properties of collagen networks, I utilize imaging techniques to isolatethe mechanics of fiber attachments at the boundaries of the system. In collaborationwith Lawrence Livermore National Lab and the Georgetown Lombardi ComprehensiveCancer Center, I investigate the polymerization and mechanical properties ofgelatin-fibrin networks. I aim to quantify the properties of biopolymer networks foruse as a novel bio-memetic 3D substrate for culture of patient derived tumor cellsand rapid parallel testing of chemotherapy protocols.
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Arevalo, Richard Carl (Georgetown University, 2013)Soft biopolymer networks undergo substantial bulk stiffening when subjected to shear strains. This nonlinear rheological signature has been well-documented for a wide range of semiflexible and stiff biopolymers, but the ...