Speaker
Description
The activation of integrins and the subsequent formation of focal complexes is a critical function in cellular sensing of ECM substrates and cell migration. Integrin adhesion complexes (IACs) allow for cell adhesion, transduce force, and signal through several pathways. While much work has been done to uncover the components and regulators involved in adhesion formation and dynamics, we have limited understanding of how individual adhesion states dictate cell motility and signaling. Without a way to dynamically control the timing, location, maturation, and disassembly of IACs, it is difficult to discern their roles at different points in their lifetime or in different locations throughout the cell. Thus, we have developed a set of optogenetic tools which allow for both the creation and manipulation of IACs in response to light. These tools allow for the rapid local induction of IACs, control of maturation, as well as the regulation of their stability and disassembly. Optogenetic IACs can be formed within seconds in the light and disassembled within minutes in the dark. These optogenetically induced adhesions signal, bear force, and dictate cell motility. Optogenetic-induced IAC formation is sufficient to polarize cells plated on fibronectin and direct cell migration. Using optical methods, we can switch between modulating adhesion maturation versus nucleation while using the same construct. By recruiting additional regulators, we can enable or disable adhesion disassembly in the light, allowing for many levels of control of adhesion dynamics. These tools enable the study of the role of adhesion formation in a direct and acute way which was not previously possible, allowing us to directly study the role of adhesion formation, its dynamics, and the role of individual proteins in IACs.
