Feeling the hidden mechanical forces in lipid bilayer is an original sense

Abstract

Life's origin entails enclosing a compartment to hoard material, energy, and information. The envelope necessarily comprises amphipaths, such as prebiotic fatty acids, to partition the two aqueous domains. The self-assembled lipid bilayer comes with a set of properties including its strong anisotropic internal forces that are chemically or physically malleable. Added bilayer stretch can alter force vectors on embedded proteins to effect conformational change. The force-from-lipid principle was demonstrated 25 y ago when stretches opened purified Escherichia coli MscL channels reconstituted into artificial bilayers. This reductionistic exercise has rigorously been recapitulated recently with two vertebrate mechanosensitive K + channels (TREK1 and TRAAK). Membrane stretches have also been known to activate various voltage-, ligand-, or Ca 2+ -gated channels. Careful analyses showed that Kv, the canonical voltage-gated channel, is in fact exquisitely sensitive even to very small tension. In an unexpected context, the canonical transient-receptor-potential channels in the Drosophila eye, long presumed to open by ligand binding, is apparently opened by membrane force due to PIP 2 hydrolysis-induced changes in bilayer strain. Being the intimate medium, lipids govern membrane proteins by physics as well as chemistry. This principle should not be a surprise because it parallels water's paramount role in the structure and function of soluble proteins. Today, overt or covert mechanical forces govern cell biological processes and produce sensations. At the genesis, a bilayer's response to osmotic force is likely among the first senses to deal with the capricious primordial sea. mechanosensitivity | force sensing | channel gating | bilayer mechanics | touch

Bilayer-thickness-mediated interactions between integral membrane proteins

“…Some discrepancy between analytic and numerical results is to be expected, given that somewhat different boundary value problems are solved in the perturbative analytic and numerical approaches, with the analytic solution only being first order in the perturbation parameter ǫ i in Eq. (16). This produces a systematic error in the thickness deformation energy obtained through the perturbative analytic approach, which yields disagreement between perturbative analytic and numerical solution procedures even in the non-interacting regime.…”

Biophysical Tools for Cellular and Subcellular Mechanical Actuation of Cell Signaling

“…The MS channel provides an evolutionarily conserved mechanism for sensing mechanical force at the membrane and it actuates by opening a pore to allow molecular transport (63). Mechanical force is sufficient to trigger a calcium wave in Drosophila oocytes from extracellular calcium entering through MS channels (64).…”

Piezo1 Channels are Inherently Mechanosensitive

“…Even in those rare cases, it is still unknown whether these channels are inherently mechanosensitive or depends on various cellular components to sense mechanical force. Cellular components that could be required for gating MS channels include auxiliary subunits, extracellular/intracellular tether proteins, specialized lipid domains such as rafts, or small molecules that are released during mechanical stimulation (Anishkin et al, 2014;Gillespie and Walker, 2001;Teng et al, 2015;Zhang et al, 2015). For example, Drosophila mechanically activated channel NOMPC has been recently shown to require cytoskeleton connection to confer mechanosensitivity (Zhang et al, 2015).…”

“…Therefore, the ultimate evidence that an ion channel is inherently mechanosensitive is to demonstrate its mechanosensitivity in a cell-free environment (Berrier et al, 2013;Brohawn et al, 2014b;Najem et al, 2015;Sukharev et al, 1994). This force transmission directly from lipids to proteins is termed the force from lipids concept (Anishkin et al, 2014;Martinac et al, 1990;Teng et al, 2015).…”

“…Heterologous expression of Piezos in cells exhibit large mechanically-activated currents, and recent reports show that Piezo1 responds to lateral membrane tension in cellular membranes (Coste et al, 2012;Cox et al, 2016;Lewis and Grandl, 2015;Ranade et al, 2015). Indeed, the roles of various cellular components that modulate Piezo channel activity are also emerging (Anishkin et al, 2014). For example, overexpressing a pathogenic mutant of Polycystin-2 (Peyronnet et al, 2013) and depletion of second messenger phosphoinositides (PIP or PIP2) inhibits mechanically activated currents in Piezo-expressing cells (Borbiro et al, 2015).…”