Session: 12-07-01: Mechanics of Soft Materials
Paper Number: 89397
89397 - Spontaneous Enlargement of Receptor Clusters in Response to Pulling Traction
Most adherent cells are capable of sensing the external forces and probing the mechanical properties of their surroundings. These are classical hallmarks of what is termed mechanotransduction. Mechanotransduction is generally attributed to the sensory functions of focal adhesion (FA) proteins upon activation by mechanical stimuli. A striking feature of cell mechanosensing is the growth of FAs in response to increased cytoskeletal or extracellular tension. Despite growing knowledge about the molecular structures of FAs, it has remained elusive as to how these anchorage points grow and how their sensory function operates. The aim of this contribution is to show that the cytoskeletal tension directly mediates the size of FAs and the number of established bonds within FAs. Within this framework, mechanotransduction is the manifestation of a thermodynamic process in cell FAs to achieve the state of minimum free energy, independent of the sensory function of molecular sensors as postulated in available models. The FA is modeled as a portion of cell membrane bound to extracellular matrix (ECM) where membrane receptors and the complementary ECM ligands can interact and form physical bonds. The receptors are assumed to be mobile that freely diffuse on the membrane and cross the boundary of the adhesion site. The membrane is covered with a thick layer of glycocalyx that forms a boundary between the membrane and ECM. The cytosolic tails of bonded receptors are linked to the actin filaments via a battery of plaque proteins that transfer the cytoskeletal tension to the ECM. By minimizing the free energy, a system of equations is derived that controls the equilibrium configuration of FAs in response to the cytoskeletal tension. The coupled equations can be solved numerically, assuming a simple geometry for the adhesion site. The results show that increasing the tension is followed by spontaneous recruitment of more receptors into the FA and establishing more bonds. Admissibility of this process is determined by the mobility of free receptors, energetic affinity between ligands and receptors, and flexibility of ligand-receptor bonds which in turn determines the mechanical work of cytoskeletal tension. If the energetic affinity between the ligands and receptors is sufficiently large, the energy released by ligation of receptors offsets the entropic penalty associated with receptor immobilization. A stability analysis shows that the stiffness of glycocalyx and rigidity of bonds are major regulators of the force-dependent size of FAs. The stretched bonds reach saddle-point bifurcation at a critical force that decreases with bond stiffness. Stronger repulsion by glycoproteins stimulates the growth of FAs in response to cytoskeletal tension.
Targeted Session: Mechano-Biology
Presenting Author: Alireza Sarvestani Mercer University
Presenting Author Biography: Alireza Sarvestani obtained his Ph.D. in Mechanical Engineering from Rensselaer Polytechnic Institute in New York. He is currently an Assistant Professor in the Department of Mechanical Engineering at Mercer University. His research interests cover different subjects in solid mechanics, composite materials, and biological adhesion.
Authors:
Alireza Sarvestani Mercer UniversityArsha Moorthy Mercer University
Spontaneous Enlargement of Receptor Clusters in Response to Pulling Traction
Paper Type
Technical Paper Publication