Date of Award
Doctor of Philosophy (PhD)
Jennifer M. Schwarz
Actin, Cytoskleton, Mechanics, Morphology
Contained in this thesis is the quest to model the growth, form and mechanics of part of the cellular cytoskeleton known as the lamellipodium. The cellular cytoskeleton is made of filamentous proteins, such as F-actin, and provides for structural support for the cell. Lamellipodia are extensions of the cellular cytoskeleton at the leading edge of a crawling cell generated so that the cell can extend, and thereby move in a particular direction. In the first two chapters, we focus on morphological characteristics of lamellipodia formation, which is, in part, shaped by branched filament nucleation via the branching protein Arp2/3. For example, we find that the orientation of filaments with respect to the leading edge of a crawling cell is optimized for filament growth. In addition, orientational and spatial degrees of freedom of the filaments are married to derive the overall shape of the filament density profile along the leading edge, another morphological characteristic. In the next two chapters, we explore the mechanics of model lamellipodia, where both freely-rotating and angle-constraining cross-linkers of actin filaments are present, in addition to the angle-constraining effect that the branching protein Arp2/3 has between mother and daughter filaments. We compare the mechanical properties of the compositely cross-linked filament networks to that of purely freely-rotating cross-linked filament networks, which has been studied by others previously. Using both theory and numerical simulations, we find that the addition of angle-constraining cross-linkers allows the lamellipodium to become rigid and transmit forces with a minimal amount of material---yet another optimization principle. Therefore, in our quest to model lamellipodia formation, we have uncovered along the way several optimization principles, which may ultimately guide, in part, our understanding of how cells crawl to heal wounds or create organs.
Quint, David Aaron, "Morphology and Mechanics of the Actin Cytoskeleton" (2011). Physics - Dissertations. 113.