RT Journal Article T1 Mechanical adaptivity of red blood cell flickering to extrinsic membrane stiffening by the solid-like biosurfactant β-Aescin A1 Hernández Moleiro, Lara A1 Herráez Aguilar, Diego A1 Solís Fernández, Guillermo A1 Caselli, Niccolo A1 Dargel, Carina A1 Dodero, Verónica I A1 Bautista Santa Cruz, José Manuel A1 Hellweg, Thomas A1 Monroy Muñoz, Francisco AB 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 dissipation PB Elsevier SN 0006-3495 YR 2025 FD 2025 LK https://hdl.handle.net/20.500.14352/119764 UL https://hdl.handle.net/20.500.14352/119764 LA eng NO Moleiro, 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.2025.03.027 NO AUTHOR 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. NO Ministerio de Ciencia, Innovación y Universidades (España) NO European Commission NO Federación Española de Enfermedades Raras NO Deutsche Forschungsgemeinschaft NO Agencia Española de Investigación AEI NO Comunidad de Madrid DS Docta Complutense RD 24 dic 2025