From H. Turlier et al. Nature Physics, 12, 513-519 (2016)
Red blood cells, or erythrocytes, are seen to
flicker under optical microscopy, a phenomenon initially described as
thermal fluctuations of the cell membrane. But recent studies have
suggested the involvement of non-equilibrium processes, without
definitively ruling out equilibrium interpretations. Using active and
passive microrheology to directly compare the membrane response and
fluctuations on single erythrocytes, we report here a violation of the
fluctuation–dissipation relation, which is a direct demonstration of the
non-equilibrium nature of flickering. With an analytical model of the
composite erythrocyte membrane and realistic stochastic simulations, we
show that several molecular mechanisms may explain the active
fluctuations, and we predict their kinetics. We demonstrate that
tangential metabolic activity in the network formed by spectrin, a
cytoskeletal protein, can generate curvature-mediated active membrane
motions. We also show that other active membrane processes represented
by direct normal force dipoles may explain the observed membrane
activity. Our findings provide solid experimental and theoretical
frameworks for future investigations of the origin and function of
active motion in cells.