Mechanical adaptivity of red blood cell flickering to extrinsic membrane stiffening by the solid-like biosurfactant β-Aescin

Hernández Moleiro, LaraHerráez Aguilar, DiegoSolís Fernández, GuillermoCaselli, NiccoloDargel, CarinaDodero, Verónica IBautista Santa Cruz, José ManuelHellweg, ThomasMonroy Muñoz, Francisco2025-04-292025-04-292025Moleiro, L. H., Herráez-Aguilar, D., Solís-Fernández, G., Caselli, N., Dargel, C., Dodero, V. I., Bautista, J. M., Hellweg, T., & Monroy, F. (2025). Mechanical adaptivity of red blood cell flickering to extrinsic membrane stiffening by the solid-like biosurfactant β-Aescin. Biophysical journal, S0006-3495(25)00200-0. Advance online publication. https://doi.org/10.1016/j.bpj.2025.03.0270006-349510.1016/j.bpj.2025.03.027https://hdl.handle.net/20.500.14352/119764AUTHOR CONTRIBUTIONS: L.H.M., D.H.A., G.S.F., N.C., V.I.D., and C.D. conducted research, provided experimental data, and contributed to analyzing data. L.H.M., J.M.B., and F.M. supervised research and drafted the manuscript. T.H. and F.M. supported the search for funding, planning the research, supervised the research, contributed to analyzing data, and wrote the manuscript.β-Aescin is a natural additive employed for treatments of vascular insufficiency, hence its impact in red blood cell (RBC) adaptivity has been conjectured. Here, we report a study about the mechanical impact of the membrane stiffener aescin on the flickering motions of live RBCs maintained at the homeostatic status. An active flickering, or nonequilibrium fluctuation dynamics has been revealed by mapping flickering motions in single RBCs treated or not with aescin. Experiments show that active RBC flickers adapt mechanically to β-escin, unlike the passive thermal fluctuations observed in lipid bilayers without an active skeleton. Mechanical connections for active flickering are theoretically argued to exist between an effective viscoelastic softness bestowed by the spectrin membrane cytoskeleton and the observed stiffness imposed by aescin as a rigidity modulator. From the unveiled diffusive mechanics, we model an adaptive RBC homeostasis that recapitulates the active flickering phenomenon as an optimal membrane softness upon a regulated friction as observed under aescin-induced membrane hardening. From a physiological perspective, RBC flicker adaptiveness to rigidization is discussed according to regulatory principles of energy conservation and minimal dissipationengAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Mechanical adaptivity of red blood cell flickering to extrinsic membrane stiffening by the solid-like biosurfactant β-Aescinjournal article1542-0086https://doi.org/10.1016/j.bpj.2025.03.02740176347open access577.1:616Bioquímica (Biología)2403 Bioquímica