Principal Investigator Roger Kamm
Actin is one of the primary protein components of the cellular cytoskeleton. By forming networks of filaments spanning considerable intracellular distances, it provides the cell with structural support. However, actin also plays central roles in cell motility, cell division and force transmission through the cell. Consequently, the dynamics of actin are pivotal to the initiation of mechanotransduction or the physio-chemical response of cells to mechanical stimuli. The varied functions of actin also mean that it has tremendous implications in medicine and disease. The dynamics of actin filament polymerization and the protein-protein interactions responsible for the regulation of the actin network have been implicated in the tumorigenisis, the pathogenesis of cardiovascular disease, bacterial infections and viral entry. Moreover, actin filaments are of keen interest as a new platform for the delivery of gene therapies and as a model material system for energy storage technology.
To understand better the remarkable behavior of filamentous actin, we investigate the mechanochemistry and dynamics of actin regulatory proteins using optical microscopy and force spectroscopy. Specifically, we are interested in learning how these proteins use mechanical signals to regulate the polymerization/de-polymerization of actin filaments at the single-molecule level.
Amyloids are fibrous protein aggregates that are the basis for many diseases such as Alzheimer’s, type 2 diabetes, Parkinsons, Huntington’s, and scrapie, among many others. It has been found however, that there are many instances of functional amyloids that are used by biology for structural purposes, such as the E. coli curli proteins and spider silk; for sensing, such as HET-s from P. anserina; or as part of a system to adapt to new environments, such as the yeast prions, eg: [PSI] (sup35).
A great deal of work has been done to characterize amyloids biochemically, genetically, and biophysically, but there is still quite a lot that is still unknown regarding the mechanisms involved in assembly of amyloid fibers and the structure of the constituent proteins in the amyloid state. We are using applied force via optical tweezers as a probe to better understand the organization of the monomers within the amyloid fibril, and to gain insight into the structure of the monomers within the fiber. The overarching goal of this project is to determine if amyloids have similar mechanical properties, and thus potentially similar organizations of the proteins within amyloid fibers.