Medical Engineering PhD Defense, Akash Dhawan

Zoom: https://caltech.zoom.us/j/83468786854
Abstract: Collagen type I is the main structural protein of the body, and it plays vital roles in various functions including wound healing, cell signaling, and force transmission. At appropriate pH, temperature, and ionic conditions, the collagen protein monomers assemble into fibrils that interweave and can trap water into a hydrogel in vitro, which has been used in wound healing applications, cell culture research, and drug delivery. Current techniques for manufacturing collagen I hydrogels allow control over macrostructural features, but have limited control over microstructural features that dictate the mechanical properties of these gels. We employed the use of a phenylglyoxylate cyclohexylammonium (PGA-CHA) photobase generator (PBG) that dissolves in acidic collagen solutions and releases a base upon interaction with light to trigger collagen assembly at physiologically relevant pH values (pH 6, 7, 8) using a single formula irradiated with 365 nm light for different durations with some spatial control via masking. Collagen gels made using the PBG showed assembly pH is directly correlated with storage modulus and inversely correlated with fibril diameter and mesh size. Fibroblasts grown on collagen gels assembled at different pH conditions using the PBG exhibited a variety of behaviors in morphology and migration, which provides insight into the length scale of mechanical properties that cells probe and the ways in which the collagen network influences cell speed and persistence. In this way, we introduce a new platform for microstructural control over collagen hydrogels using a PBG, which may be useful in influencing cells through their mechanical environment.

Advisor: Professor Julia Kornfield