Mechanical
Signaling
Molecular Forces
This area of inquiry seeks to delineate the role of atomic and molecular forces to define mechanobiology at cellular levels. The process of force transmission through the lipid bilayer remains at best partially-understood and the nature of the forces developed and exerted at the cell or tissue level remain a fundamental area of inquiry.
Mechanosensitive Channels
Our center pursues close examination of the mechanisms associated with force form lipids signaling in excitable cells, where lipid-protein interaction define the function of many mechanosensitive channels, from prokaryotes to humans. The better understanding of these forces and the molecular machines that underlie them can allow the development of the mechanoelectrical building blocks required for future bioengineering developments.
Molecular mechanisms for the activation of mechanosensitive adhesion receptors
One of our focuses is to understand the activation mechanisms of critical mechanosensitive cell-adhesion receptors called adhesion G protein-coupled receptors (aGPCRs). These receptors respond to mechanical forces that are applied on their extracellular regions on the cell surface; they help cells respond to such mechanical stimuli by activating intracellular signaling pathways.
Recently, the Araç Lab revealed the first three-dimensional cryo-EM structure of a holo-aGPCR which provided clues for signal transduction from outside-to-inside the cell. They also use optical tweezers, which serve as tools to understand how aGPCRs respond to different types of applied force.
Mechanosensitive cell-surface receptors
Defining the key biochemical and biophysical properties of mechanosensitive receptors is key not only to understand how they work but also to manipulate them for the treatment of diseases.
This area focuses on characterizing understudied mechanosensitive adhesion G protein-coupled receptors. The Araç Lab has made recent breakthroughs in understanding the three-dimensional architecture and regulatory modes of CELSRs, molecules important for lymphatic fluid flow as well as cerebrospinal fluid flow among many other processes.
CELSRs are crucial in several biological situations where shear stress is present so they likely have a mechanism to respond to it.
Being able to see the extracellular and transmembrane regions of aGPCRs directly communicating opens ways for unlocking several new drug targets!
