Equilibrium physics breakdown reveals the active nature of red blood cell flickering

Turlier, Hervé; Fedosov, Dmitry; Audoly, Basile; Auth, Thorsten; Gov, Nir S.; Sykes, Cécile; Joanny, Jean‐François; Gompper, Gerhard; Betz, Timo

doi:10.1038/nphys3621

Cited by 265 publications

(343 citation statements)

References 65 publications

(106 reference statements)

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“…Here, we neglect interesting nonequilibrium effects in living cells, where ATP can be burned to turn spectrin into an "active" material [86]. Note that by treating red blood cells with mild detergents, which lyse the cells, one can produce red blood cell "ghosts" that are composed of spectrin skeleton alone.…”

Section: Discussionmentioning

confidence: 99%

Statistical Mechanics of Thin Spherical Shells

Košmrlj

Nelson

2017

Phys. Rev. X

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We explore how thermal fluctuations affect the mechanics of thin amorphous spherical shells. In flat membranes with a shear modulus, thermal fluctuations increase the bending rigidity and reduce the inplane elastic moduli in a scale-dependent fashion. This is still true for spherical shells. However, the additional coupling between the shell curvature, the local in-plane stretching modes, and the local out-ofplane undulations leads to novel phenomena. In spherical shells, thermal fluctuations produce a radiusdependent negative effective surface tension, equivalent to applying an inward external pressure. By adapting renormalization group calculations to allow for a spherical background curvature, we show that while small spherical shells are stable, sufficiently large shells are crushed by this thermally generated "pressure." Such shells can be stabilized by an outward osmotic pressure, but the effective shell size grows nonlinearly with increasing outward pressure, with the same universal power-law exponent that characterizes the response of fluctuating flat membranes to a uniform tension.

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Section: Discussionmentioning

confidence: 99%

Statistical Mechanics of Thin Spherical Shells

Košmrlj

Nelson

2017

Phys. Rev. X

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“…24 The confinement is also passive in the sense that no active immobilization by optical tweezers is needed, eliminating corresponding photo-degradation or spurious photoinduced effects that inherently prohibit the access to reversible or long-term experiments on single functional RBCs. The accumulated radiation dose introduced through high-intensity trapping lasers can lead to hemolysis of RBCs 10 or induces the conversion of oxyHb to the inactive metHb state, 18 both limiting the information that can be acquired by either microscopic or spectroscopic techniques. Our approach overcomes this limitation and combined with confocal resonance Raman spectroscopy we were able to record Raman spectra of functional individual RBCs purely in the oxyHb state.…”

Section: Discussionmentioning

confidence: 99%

“…10 Using our specialized device, the time-resolved analysis of a single RBC's morphological response with its related alterations of the membrane edge fluctuation amplitude shows a timescale of about 10 min. This is significantly slower than the change in osmolarity at the RBC's position inside the microchamber via diffusive washing.…”

Section: Rbc Diffusive Behavior and Membrane Edge Fluctuationsmentioning

confidence: 99%

“…24 Alternative methods use active immobilization of single RBCs by optical tweezers in order to avoid adsorption-induced effects due to chemical fixation. However, the required high-intensity trapping lasers can already induce hemolysis, 10 and the stress levels introduced on the RBC often represent the limiting factor in acquiring information of which the experiment is actually aiming for. 18 Here, we present a self-filling microfluidic device for single RBC assays starting directly with unprocessed, small volume human blood samples.…”

Section: Introductionmentioning

confidence: 99%

“…4 Especially, the vibratory motions of the RBC's plasma membrane, referred to as "flickering," 5 have been related to its biomechanical properties, which have been studied extensively in both single-cell experiments and theoretical work. [6][7][8][9][10] Moreover, the membrane fluctuations may also control adhesive phenomena, such as rouleau formation. 8 The presence of rouleaux is a cause of bloodrelated disorders and there are many pathological cases like malaria or sickle cell anemia where RBCs form these large aggregates that hinder blood flow.…”

Section: Introductionmentioning

confidence: 99%

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A self-filling microfluidic device for noninvasive and time-resolved single red blood cell experiments

et al. 2016

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Existing approaches to red blood cell (RBC) experiments on the single-cell level usually rely on chemical or physical manipulations that often cause difficulties with preserving the RBC's integrity in a controlled microenvironment. Here, we introduce a straightforward, self-filling microfluidic device that autonomously separates and isolates single RBCs directly from unprocessed human blood samples and confines them in diffusion-controlled microchambers by solely exploiting their unique intrinsic properties. We were able to study the photo-induced oxygenation cycle of single functional RBCs by Raman microscopy without the limitations typically observed in optical tweezers based methods. Using bright-field microscopy, our noninvasive approach further enabled the time-resolved analysis of RBC flickering during the reversible shape evolution from the discocyte to the echinocyte morphology. Due to its specialized geometry, our device is particularly suited for studying the temporal behavior of single RBCs under precise control of their environment that will provide important insights into the RBC's biomedical and biophysical properties. Published by AIP Publishing. [http://dx

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Modeling cytoadhesion of Plasmodium falciparum‐infected erythrocytes and leukocytes—common principles and distinctive features

et al. 2016

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Cytoadhesion of Plasmodium falciparum‐infected erythrocytes to the microvascular endothelial lining shares striking similarities to cytoadhesion of leukocytes. In both cases, adhesins are presented in structures that raise them above the cell surface. Another similarity is the enhancement of adhesion under physical force (catch bonding). Here, we review recent advances in our understanding of the molecular and biophysical mechanisms underlying cytoadherence in both cellular systems. We describe how imaging, flow chamber experiments, single‐molecule measurements, and computational modeling have been used to decipher the relevant processes. We conclude that although the parasite seems to induce processes that resemble the cytoadherence of leukocytes, the mechanics of erythrocytes is such that the resulting behavior in shear flow is fundamentally different.

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Equilibrium physics breakdown reveals the active nature of red blood cell flickering

Cited by 265 publications

References 65 publications

Statistical Mechanics of Thin Spherical Shells

Statistical Mechanics of Thin Spherical Shells

A self-filling microfluidic device for noninvasive and time-resolved single red blood cell experiments

Modeling cytoadhesion of Plasmodium falciparum‐infected erythrocytes and leukocytes—common principles and distinctive features

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