arXiv subjects

Thomas Risler

Publications and source records attributed to Thomas Risler.

18 recordsLinked to original sources

arXiv2022

Spontaneous flow created by active topological defects

Topological defects are at the root of the large-scale organization of liquid crystals. In two-dimensional active nematics, two classes of topological defects of charges $\pm 1/2$ are known to play a major role due to active stresses. Despite this importance, few analytical results have been obtained on the flow-field and active-stress patterns around active topological defects. Using the generic hydrodynamic theory of active systems, we investigate the flow and stress patterns around these topological defects in unbounded, two-dimensional active nematics. Under generic assumptions, we derive analytically the spontaneous velocity and stall force of self-advected defects in the presence of both shear and rotational viscosities. Applying our formalism to the dynamics of monolayers of elongated cells at confluence, we show that the non-conservation of cell number generically increases the self-advection velocity and could provide an explanation for their observed role in cellular extrusion and multilayering. We finally investigate numerically the influence of the Ericksen stress. Our work paves the way to a generic study of the role of topological defects in active nematics, and in particular in monolayers of elongated cells.

cond-mat.soft↗

arXiv2021

Viscocapillary Instability in Cellular Spheroids

We describe a viscocapillary instability that can perturb the spherical symmetry of cellular aggregates in culture, also called multicellular spheroids. In the condition where the cells constituting the spheroid get their necessary metabolites from the immediate, outer microenvironment, a permanent cell flow exists within the spheroid from its outer rim where cells divide toward its core where they die. A perturbation of the spherical symmetry induces viscous shear stresses within the tissue that can destabilise the aggregate. The proposed instability is viscocapillary in nature and does not rely on external heterogeneities, such as a pre-existing pattern of blood vessels or the presence of a substrate on which the cells can exert pulling forces. It arises for sufficiently large cell-cell adhesion strengths, cell-renewal rates, and metabolite supplies, as described by our model parameters. Since multicellular spheroids in culture are good model systems of small, avascular tumours, mimicking the metabolite concentration gradients found in vivo, we can speculate that our description applies to microtumour instabilities in cancer progression.

physics.bio-ph↗

arXiv2017

Lipid bilayer mediates ion-channel cooperativity in a model of hair-cell mechanotransduction

Mechanoelectrical transduction in the inner ear is a biophysical process underlying the senses of hearing and balance. The key players involved in this process are mechanosensitive ion channels. They are located in the stereocilia of hair cells and opened by the tension in specialized molecular springs, the tip links, connecting adjacent stereocilia. When channels open, the tip links relax, reducing the hair-bundle stiffness. This gating compliance makes hair cells especially sensitive to small stimuli. The classical explanation for the gating compliance is that the conformational rearrangement of a single channel directly shortens the tip link. However, to reconcile theoretical models based on this mechanism with experimental data, an unrealistically large structural change of the channel is required. Experimental evidence indicates that each tip link is a dimeric molecule, associated on average with two channels at its lower end. It also indicates that the lipid bilayer modulates channel gating, although it is not clear how. Here, we design and analyze a model of mechanotransduction where each tip link attaches to two channels, mobile within the membrane. Their states and positions are coupled by membrane-mediated elastic forces arising from the interaction between the channels' hydrophobic cores and that of the lipid bilayer. This coupling induces cooperative opening and closing of the channels. The model reproduces the main properties of hair-cell mechanotransduction using only realistic parameters constrained by experimental evidence. This work provides an insight into the fundamental role that membrane-mediated ion-channel cooperativity can play in sensory physiology.

q-bio.SC↗

arXiv2015

Homeostatic Fluctuations of a Tissue Surface

We study the surface fluctuations of a tissue with a dynamics dictated by cell-rearrangement, cell-division, and cell-death processes. Surface fluctuations are calculated in the homeostatic state, where cell division and cell death equilibrate on average. The obtained fluctuation spectrum can be mapped onto several other spectra such as those characterizing incompressible fluids, compressible Maxwell elastomers, or permeable membranes in appropriate asymptotic regimes. Since cell division and cell death are out-of-equilibrium processes, detailed balance is broken, but a generalized fluctuation-response relation is satisfied in terms of appropriate observables. Our work is a first step toward the description of the out-of-equilibrium fluctuations of the surface of a thick epithelium and its dynamical response to external perturbations.

physics.bio-ph↗

arXiv2015

Focus on the Physics of Cancer

Despite the spectacular achievements of molecular biology in the second half of the twentieth century and the crucial advances it permitted in cancer research, the fight against cancer has brought some disillusions. It is nowadays more and more apparent that getting a global picture of the very diverse and interlinked aspects of cancer development necessitates, in synergy with these achievements, other perspectives and investigating tools. In this undertaking, multidisciplinary approaches that include quantitative sciences in general and physics in particular play a crucial role. This `focus on' collection contains 19 articles representative of the diversity and state-of-the-art of the contributions that physics can bring to the field of cancer research.

physics.bio-ph↗

arXiv2015

Damping Properties of the Hair Bundle

The viscous liquid surrounding a hair bundle dissipates energy and dampens oscillations, which poses a fundamental physical challenge to the high sensitivity and sharp frequency selectivity of hearing. To identify the mechanical forces at play, we constructed a detailed finite-element model of the hair bundle. Based on data from the hair bundle of the bullfrog's sacculus, this model treats the interaction of stereocilia both with the surrounding liquid and with the liquid in the narrow gaps between the individual stereocilia. The investigation revealed that grouping stereocilia in a bundle dramatically reduces the total drag. During hair-bundle deflections, the tip links potentially induce drag by causing small but very dissipative relative motions between stereocilia; this effect is offset by the horizontal top connectors that restrain such relative movements at low frequencies. For higher frequencies the coupling liquid is sufficient to assure that the hair bundle moves as a unit with a low total drag. This work reveals the mechanical characteristics originating from hair-bundle morphology and shows quantitatively how a hair bundle is adapted for sensitive mechanotransduction.

q-bio.SC↗

arXiv2015

Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly

Epithelial spreading is a common and fundamental aspect of various developmental and disease-related processes such as epithelial closure and wound healing. A key challenge for epithelial tissues undergoing spreading is to increase their surface area without disrupting epithelial integrity. Here we show that orienting cell divisions by tension constitutes an efficient mechanism by which the Enveloping Cell Layer (EVL) releases anisotropic tension while undergoing spreading during zebrafish epiboly. The control of EVL cell-division orientation by tension involves cell elongation and requires myosin II activity to align the mitotic spindle with the main tension axis. We also found that in the absence of tension-oriented cell divisions and in the presence of increased tissue tension, EVL cells undergo ectopic fusions, suggesting that the reduction of tension anisotropy by oriented cell divisions is required to prevent EVL cells from fusing. We conclude that cell-division orientation by tension constitutes a key mechanism for limiting tension anisotropy and thus promoting tissue spreading during EVL epiboly.

q-bio.TO↗

arXiv2015

A Reaction-Diffusion Model of the Cadherin-Catenin System: A Possible Mechanism for Contact Inhibition and Implications for Tumorigenesis

Contact inhibition is the process by which cells switch from a motile growing state to a passive and stabilized state upon touching their neighbors. When two cells touch, an adhesion link is created between them by means of transmembrane E-cadherin proteins. Simultaneously, their actin filaments stop polymerizing in the direction perpendicular to the membrane and reorganize to create an apical belt that colocalizes with the adhesion links. Here, we propose a detailed quantitative model of the role of the cytoplasmic $β$-catenin and $α$-catenin proteins in this process, treated as a reaction-diffusion system. Upon cell-cell contact, the concentration in $α$-catenin dimers increases, inhibiting actin branching and thereby reducing cellular motility and expansion pressure. This model provides a mechanism for contact inhibition that could explain previously unrelated experimental findings on the role played by E-cadherin, $β$-catenin and $α$-catenin in the cellular phenotype and in tumorigenesis. In particular, we address the effect of a knockout of the adenomatous polyposis coli tumor suppressor gene. Potential direct tests of our model are discussed.

physics.bio-ph↗

arXiv2013

Morphological instabilities of stratified epithelia: a mechanical instability in tumour formation

Interfaces between stratified epithelia and their supporting stromas commonly exhibit irregular shapes. Undulations are particularly pronounced in dysplastic tissues and typically evolve into long, finger-like protrusions in carcinomas. In a previous work (Basan et al., Phys. Rev. Lett. 106, 158101 (2011)), we demonstrated that an instability arising from viscous shear stresses caused by the constant flow due to cell turnover in the epithelium could drive this phenomenon. While interfacial tension between the two tissues as well as mechanical resistance of the stroma tend to maintain a flat interface, an instability occurs for sufficiently large viscosity, cell-division rate and thickness of the dividing region in the epithelium. Here, extensions of this work are presented, where cell division in the epithelium is coupled to the local concentration of nutrients or growth factors diffusing from the stroma. This enhances the instability by a mechanism similar to that of the Mullins-Sekerka instability in single-diffusion processes of crystal growth. We furthermore present the instability for the generalized case of a viscoelastic stroma.

physics.bio-ph↗

arXiv2012

Relative stereociliary motion in a hair bundle opposes amplification at distortion frequencies

Direct gating of mechanoelectrical-transduction channels by mechanical force is a basic feature of hair cells that assures fast transduction and underpins the mechanical amplification of acoustic inputs. But the associated nonlinearity - the gating compliance - inevitably distorts signals. Because reducing distortion would make the ear a better detector, we sought mechanisms with that effect. Mimicking in vivo stimulation, we used stiff probes to displace individual hair bundles at physiological amplitudes and measured the coherence and phase of the relative stereociliary motions with a dual-beam differential interferometer. Although stereocilia moved coherently and in phase at the stimulus frequencies, large phase lags at the frequencies of the internally generated distortion products indicated dissipative relative motions. Tip links engaged these relative modes and decreased the coherence in both stimulated and free hair bundles. These results show that a hair bundle breaks into a highly dissipative serial arrangement of stereocilia at distortion frequencies, precluding their amplification.

q-bio.SC↗

arXiv2012

Forces between clustered stereocilia minimize friction in the ear on a subnanometre scale

The detection of sound begins when energy derived from acoustic stimuli deflects the hair bundles atop hair cells. As hair bundles move, the viscous friction between stereocilia and the surrounding liquid poses a fundamental challenge to the ear's high sensitivity and sharp frequency selectivity. Part of the solution to this problem lies in the active process that uses energy for frequency-selective sound amplification. Here we demonstrate that a complementary part involves the fluid-structure interaction between the liquid within the hair bundle and the stereocilia. Using force measurement on a dynamically scaled model, finite-element analysis, analytical estimation of hydrodynamic forces, stochastic simulation and high-resolution interferometric measurement of hair bundles, we characterize the origin and magnitude of the forces between individual stereocilia during small hair-bundle deflections. We find that the close apposition of stereocilia effectively immobilizes the liquid between them, which reduces the drag and suppresses the relative squeezing but not the sliding mode of stereociliary motion. The obliquely oriented tip links couple the mechanotransduction channels to this least dissipative coherent mode, whereas the elastic horizontal top connectors stabilize the structure, further reducing the drag. As measured from the distortion products associated with channel gating at physiological stimulation amplitudes of tens of nanometres, the balance of forces in a hair bundle permits a relative mode of motion between adjacent stereocilia that encompasses only a fraction of a nanometre. A combination of high-resolution experiments and detailed numerical modelling of fluid-structure interactions reveals the physical principles behind the basic structural features of hair bundles and shows quantitatively how these organelles are adapted to the needs of sensitive mechanotransduction.

q-bio.SC↗

arXiv2011

Stress Clamp Experiments on Multicellular Tumor Spheroids

The precise role of the microenvironment on tumor growth is poorly understood. Whereas the tumor is in constant competition with the surrounding tissue, little is known about the mechanics of this interaction. Using a novel experimental procedure, we study quantitatively the effect of an applied mechanical stress on the long-term growth of a spheroid cell aggregate. We observe that a stress of 10 kPa is sufficient to drastically reduce growth by inhibition of cell proliferation mainly in the core of the spheroid. We compare the results to a simple numerical model developed to describe the role of mechanics in cancer progression.

physics.bio-ph↗

arXiv2011

Cytoskeleton and Cell Motility

The present article is an invited contribution to the Encyclopedia of Complexity and System Science, Robert A. Meyers Ed., Springer New York (2009). It is a review of the biophysical mechanisms that underly cell motility. It mainly focuses on the eukaryotic cytoskeleton and cell-motility mechanisms. Bacterial motility as well as the composition of the prokaryotic cytoskeleton is only briefly mentioned. The article is organized as follows. In Section III, I first present an overview of the diversity of cellular motility mechanisms, which might at first glance be categorized into two different types of behaviors, namely "swimming" and "crawling". Intracellular transport, mitosis - or cell division - as well as other extensions of cell motility that rely on the same essential machinery are briefly sketched. In Section IV, I introduce the molecular machinery that underlies cell motility - the cytoskeleton - as well as its interactions with the external environment of the cell and its main regulatory pathways. Sections IV D to IV F are more detailed in their biochemical presentations; readers primarily interested in the theoretical modeling of cell motility might want to skip these sections in a first reading. I then describe the motility mechanisms that rely essentially on polymerization-depolymerization dynamics of cytoskeleton filaments in Section V, and the ones that rely essentially on the activity of motor proteins in Section VI. Finally, Section VII is devoted to the description of the integrated approaches that have been developed recently to try to understand the cooperative phenomena that underly self-organization of the cell cytoskeleton as a whole.

physics.bio-ph↗

arXiv2011

Undulation Instability of Epithelial Tissues

Treating the epithelium as an incompressible fluid adjacent to a viscoelastic stroma, we find a novel hydrodynamic instability that leads to the formation of protrusions of the epithelium into the stroma. This instability is a candidate for epithelial fingering observed in vivo. It occurs for sufficiently large viscosity, cell-division rate and thickness of the dividing region in the epithelium. Our work provides physical insight into a potential mechanism by which interfaces between epithelia and stromas undulate, and potentially by which tissue dysplasia leads to cancerous invasion.

physics.bio-ph↗

arXiv2009

Coherent motion of stereocilia assures the concerted gating of hair-cell transduction channels

The hair cell's mechanoreceptive organelle, the hair bundle, is highly sensitive because its transduction channels open over a very narrow range of displacements. The synchronous gating of transduction channels also underlies the active hair-bundle motility that amplifies and tunes responsiveness. The extent to which the gating of independent transduction channels is coordinated depends on how tightly individual stereocilia are constrained to move as a unit. Using dual-beam interferometry in the bullfrog's sacculus, we found that thermal movements of stereocilia located as far apart as a bundle's opposite edges display high coherence and negligible phase lag. Because the mechanical degrees of freedom of stereocilia are strongly constrained, a force applied anywhere in the hair bundle deflects the structure as a unit. This feature assures the concerted gating of transduction channels that maximizes the sensitivity of mechanoelectrical transduction and enhances the hair bundle's capacity to amplify its inputs.

q-bio.SC↗

arXiv2009

Universal critical behavior of noisy coupled oscillators: A renormalization group study

We show that the synchronization transition of a large number of noisy coupled oscillators is an example for a dynamic critical point far from thermodynamic equilibrium. The universal behaviors of such critical oscillators, arranged on a lattice in a $d$-dimensional space and coupled by nearest neighbors interactions, can be studied using field theoretical methods. The field theory associated with the critical point of a homogeneous oscillatory instability (or Hopf bifurcation of coupled oscillators) is the complex Ginzburg-Landau equation with additive noise. We perform a perturbative renormalization group (RG) study in a $4-ε$ dimensional space. We develop an RG scheme that eliminates the phase and frequency of the oscillations using a scale-dependent oscillating reference frame. Within a Callan-Symanzik RG scheme to two-loop order in perturbation theory, we find that the RG fixed point is formally related to the one of the model $A$ dynamics of the real Ginzburg-Landau theory with an O(2) symmetry of the order parameter. Therefore, the dominant critical exponents for coupled oscillators are the same as for this equilibrium field theory. This formal connection with an equilibrium critical point imposes a relation between the correlation and response functions of coupled oscillators in the critical regime. Since the system operates far from thermodynamic equilibrium, a strong violation of the fluctuation-dissipation relation occurs and is characterized by a universal divergence of an effective temperature. The formal relation between critical oscillators and equilibrium critical points suggests that long-range phase order exists in critical oscillators above two dimensions.

cond-mat.stat-mech↗

arXiv2009

Homeostatic competition drives tumor growth and metastasis nucleation

We propose a mechanism for tumor growth emphasizing the role of homeostatic regulation and tissue stability. We show that competition between surface and bulk effects leads to the existence of a critical size that must be overcome by metastases to reach macroscopic sizes. This property can qualitatively explain the observed size distributions of metastases, while size-independent growth rates cannot account for clinical and experimental data. In addition, it potentially explains the observed preferential growth of metastases on tissue surfaces and membranes such as the pleural and peritoneal layers, suggests a mechanism underlying the seed and soil hypothesis introduced by Stephen Paget in 1889 and yields realistic values for metastatic inefficiency. We propose a number of key experiments to test these concepts. The homeostatic pressure as introduced in this work could constitute a quantitative, experimentally accessible measure for the metastatic potential of early malignant growths.

q-bio.TO↗

arXiv2004

Universal Critical Behavior of Noisy Coupled Oscillators

We study the universal thermodynamic properties of systems consisting of many coupled oscillators operating in the vicinity of a homogeneous oscillating instability. In the thermodynamic limit, the Hopf bifurcation is a dynamic critical point far from equilibrium described by a statistical field theory. We perform a perturbative renormalization group study, and show that at the critical point a generic relation between correlation and response functions appears. At the same time the fluctuation-dissipation relation is strongly violated.

cond-mat.stat-mech↗