UC Berkeley

The last decade has seen exciting and unprecedented work at the interface between biology and materials science, particularly in the form of exquisite control of cell attachment, shape, traction, motility, and differentiation. Recent progress in developing techniques for microfabrication of biomaterials helps recapitulate many extracellular matrix (ECM) cues, making them progressively more useful for applications in biology and tissue engineering. This dissertation presents a study of femtosecond laser assisted micro- and nano-fabrication applicable for the biomaterials design aiming at achieving deliberate control of the cell behavior. Cell mechanics connected to cell alignment and migration, from speculation of cell response to the biomaterials surface to control of the response by topographic and chemical patterns, was studied.

Cell migration is an essential cellular process for a variety of physiological and pathological phenomena. Migration of leukocytes mediates phagocytic and immune responses. Migration of fibroblasts, vascular endothelial cells, and osteoblasts contributes to wound healing and tissue regeneration, and tumor cell migration is essential to metastasis. The cell migration process can be initiated by mechanical and chemical cues from the extracellular microenvironment. Factors affecting cell migration can be both soluble and insoluble macromolecules that comprise the ECM or mediate extracellular communication.

We apply femtosecond laser induced two-photon polymerization and multiphoton laser ablation lithography to fabricate precisely defined two-dimensional patterned surface in nanometer to micrometer length scale and three-dimensional filamentous materials to be used in studies addressing fundamental issues concerning control of cell adhesion and migration. We studied microscale topographical patterned surface for cell alignment and migration. Anisotropic micronscale ridge/groove patterned surfaces are powerful cues to control cell shape and to enhance or obstruct cell migration. However, they have limited ability to independently control the size and the distribution of the cell adhesive domains and the ligand density. Thus, we applied chemically and topographically patterned surfaces in the nanoscale to control cell adhesion and guide directional cell migration to overcome constraints of microscale patterns. During cell migration, contractile force is needed to move the cell body forward. We also studied the contractile force exerted by an individual locomoting cell using fiber scaffolds.