Biology subjects

Duprez, G.

Publications and source records attributed to Duprez, G..

3 recordsLinked to original sources

bioRxiv2025

Control of cellular cortical tension and shape by RhoGTPase signalling

Shape changes are ubiquitous in biology, from cytokinesis at the single cell scale to tissue-scale morphogenesis involving coordinated changes in hundreds of cells. In all cases, morphogenesis is powered by gradients in mechanical tension that arise downstream of signalling. Many pathways converge on RhoGTPases that modulate the cytoskeleton and cell contractility to control cell mechanics and, subsequently, shape. Despite their physiological importance, we lack a quantitative understanding of how changes in signalling alter cortical mechanics to drive cell shape change. Here, we use optogenetics to quantitatively characterise the relationship between the amount of RhoGEF localised to the membrane, the downstream myosin recruitment, and the subsequent mechanical changes. We then show that cortical myosin amount and cortical tension increase linearly with the amount of membranous RhoGEF signalling. Based on these data, we develop a predictive model of the temporal evolution of RhoGEF membrane localisation, cortical myosin enrichment, and cortical tension in response to a pulse of light. Using this model together with an active surface model of the cell cortex, we show that the cellular shape changes induced by localised optogenetic recruitment of RhoGEF signalling can be predicted, directly linking gradients in signalling to shape change. Significance statementShape changes are ubiquitous in biology, during division in single cells and in tissue during embryogenesis. In all cases, shape change is powered by gradients in mechanical tension that arise downstream of changes in biochemical signals. Despite their importance, we lack a quantitative understanding of how changes in signals alter cell mechanics to drive cell shape change. Here, we control the location and amount of biochemical signal using light to quantitatively characterise the relationship between signals and their resulting biological and mechanical changes. We show that mechanical change scales linearly with the amount of biochemical signal. Based on this, we develop a mathematical model that predicts cell mechanical and shape changes from the location and amount of biochemical signals.

biophysics↗

bioRxiv2025

Transient volume stabilization reveals the key role a PM permeability in pyroptotic cell swelling.

Pyroptosis, an inflammatory form of cell death, is characterized by massive cell swelling and plasma membrane rupture. Although swelling was recently shown to occur in two steps, the molecular and biophysical mechanisms driving this process remained unclear. Using fast quantitative microscopy, we reveal that between the two swelling phases, cell volume transiently stabilizes despite sustained plasma membrane permeability to ions and small molecules. From a biophysical perspective, the existence of such a plateau is puzzling, as ion pumps should not be able to regulate cell volume under these conditions. To address this, we developed a physical model based on an ion pump and leak framework that incorporates the dynamics of non-selective pore formation. Experimentally, we demonstrate that the plateau phase is controlled by the dynamics of the GSDMD pore enlargement, which is modulated by Ninj1 activation, possibly through intracellular calcium. Ninj1-mediated lesions are also required for the second swelling phase. We further show that fully opened GSDMD pores display an effective hydrodynamic radius slightly above 1.9 nm, providing an insitu upper bound for pore size. Together, our findings demonstrate that pyroptotic volume dysregulation emerges from the successive and interdependent actions of GSDMD and Ninj1, each imparting distinct permeability regimes associated with increased water filtration and decreased ion selectivity due to pore opening. These insights bridge molecular and biophysical perspectives on lytic cell death and may inform the broader understanding of membrane rupture in inflammatory and pathological contexts. Significance StatementAmong programmed modes of lytic cell death, pyroptosis mediated by gasdermin D (GSDMD) and ninjurin-1 (Ninj1) involves dramatic changes in cell shape and large volume fluctuations, fundamentally altering the cells physical properties. By combining optogenetics, quantitative microscopy, and modeling, we show that a progressive increase in plasma membrane pore size drives cell swelling and membrane lysis through successive and interdependent actions of GSDMD and Ninj1, each imparting distinct permeability regimes associated with increased water filtration and decreased ion selectivity. A deeper understanding of these dynamic cell modifications will shed light on the molecular and biophysical mechanisms driving different forms of cell death.

biophysics↗

bioRxiv2023

Anisotropic Subcutaneous Response During Fingertip Normal and Tangential Loadings

The subcutaneous mechanical response of the fingertip is highly anisotropic due to the presence of a network of collagen fibers linking the outer skin layer to the bone. Yet, the impact of this anisotropy on the fingerpad deformation had not been studied until now. This issue is here tackled using a two-dimensional finite element model of a transverse section of the finger. Different hypotheses about the orientation of the fibers are considered: radial (physiologic), circumferential, and random (isotropic behavior). The three variants of the model are assessed using experimental observations of a finger leaning on a flat surface. Predictions relying on the physiological orientation of fibers align best with reality. Moreover, the orientation of fibers plays a crucial role in determining the distribution of internal strain and stress. These factors, combined with the abrupt shift in contact pressure during the transition from sticking to slipping, represent important sensory cues for partial slip detection. This is valuable information for the development of haptic devices.

bioengineering↗