Tiny Forces from Flow Transport Membrane Proteins on Cell Surfaces

Many cells sense and respond to flow in their environment, and flow responses regulate important physiological processes such as blood pressure. A paradox in cardiovascular flow sensing is that shear forces applied by blood flow are extremely small, and it is currently unknown how cells detect them. We propose a mechanical solution to this problem: lipid-anchored membrane proteins can be rearranged even by tiny shear forces. We have previously shown that avidin linked to biotinylated lipids in supported membranes forms micron-scale concentration gradients in response to femtonewton-sized shear forces. We observe that in both living cells and glass-supported lipid bilayers, proteins move downstream when flow is on, forming a concentration gradient, and that the gradient disappears when the flow is turned off. This gradient is responsive to flow magnitude and direction and disappears when flow stops. We estimate protein diffusion constants and hydrodynamic areas by observing the gradient dynamics. Our recent work demonstrates the sensitivity of our method for measuring these forces, allowing us to correlate hydrodynamic force with the folded shape of lipid-anchored proteins, distinguish membrane drag on different lipid anchors, and demonstrate that similar protein transport can occur on the surface of living cells. Our results support the hypothesis that lateral transport of membrane proteins may contribute to flow sensing.