Abstract
The sensing of physical force, mechanosensation, underlies two of five human senses—touch and hearing. How transduction of force in a membrane occurs remains unclear. We asked if a biological membrane could employ kinetic energy to transduce a signal absent tension. Here we show that lipid rafts are dynamic compartments that inactivate the signalling enzyme phospholipase D2 (PLD2) by sequestering the enzyme from its substrate. Mechanical disruption of the lipid rafts activates PLD2 by mixing the enzyme with its substrate to produce the signalling lipid phosphatidic acid (PA). We calculate a latency time of <650 μs for PLD activation by mixing. Our results establish a fast, non-tension mechanism for mechanotransduction where disruption of ordered lipids initiates a mechanosensitive signal for cell growth through mechanical mixing.
Highlights
The sensing of physical force, mechanosensation, underlies two of five human senses—touch and hearing
As no system is perfectly elastic, a component of applied force must dissipate in the form of kinetic energy, raising the following questions: how much kinetic force is required to perturb a biological membrane and how does this energy affect the plasma membrane and mechanosensitive proteins?
In order to understand the dynamics of these lipid rafts and ascertain their suitability as mechanosensors in the plasma membrane of C2C12 cells, we examined the dwell time and lateral movement of cholesterol rafts in real time using high-resolution 3D-dSTORM imaging on live cells
Summary
The sensing of physical force, mechanosensation, underlies two of five human senses—touch and hearing. The plasma membrane is thought to couple force directly with effector molecules such as mechanosensitive ion channels[3,4,5] and organize mechanosensitive proteins including focal adhesion proteins[6]. These mechanosensitive proteins often reside compartmentalized within or outside of lipid rafts[7]. Since signalling lipids and mechanosensitive proteins often reside compartmentalized within or outside of lipid rafts[7], we hypothesized that force-induced mixing of lipid compartments in a biological membrane could activate a mechanosensitive protein and transduce a biological signal. If an enzyme resides in a raft and the enzyme’s substrate resides outside of a raft, mechanical disruption of the raft exposes the enzyme to its substrate producing a mechanically activated signal (see Fig. 1b)
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