Aspiration of biological viscoelastic drops

Spherical cellular aggregates are in vitro systems to study the physical and biophysical properties of tissues. We present a novel approach to characterize the mechanical properties of cellular aggregates using micropipette aspiration technique. We observe an aspiration in two distinct regimes, a fast elastic deformation followed by a viscous flow. We develop a model based on this viscoelastic behavior to deduce the surface tension, viscosity, and elastic modulus. A major result is the increase of the surface tension with the applied force, interpreted as an effect of cellular mechanosensing.Comment: 4 pages, 4 figures

Probing Gravitational Sensitivity in Biological Systems Using Magnetic Body Forces

At Brown University, we are developing the use of magnetic body forces as a means to simulate variable gravity body forces on biological systems. This tool promises new means to probe gravi-sensing and the gravi-response of biological systems. It also has the potential as a technique for screening future systems for space flight experiments

Rectified random cell motility as a mechanism for embryo elongation

The body of vertebrate embryos forms by posterior elongation from a terminal growth zone called the tail bud. The tail bud is a source of highly motile cells that eventually constitute the presomitic mesoderm (PSM), a tissue that plays an important role in elongation movements. PSM cells establish an anterior-posterior cell motility gradient that parallels a gradient associated with the degradation of a specific cellular signal (FGF) known to be implicated in cell motility. Here, we combine the electroporation of fluorescent reporters in the PSM with time-lapse imaging in the chicken embryo to quantify cell diffusive movements along the motility gradient. We show that a simple microscopic model for random cell motility induced by FGF activity along with geometric confinement leads to rectified tissue elongation consistent with our observations. A continuum analog of the microscopic model leads to a macroscopic mechano-chemical model for tissue extension that couples FGF activity-induced cell motility and tissue rheology, and is consistent with the experimentally observed speed and extent of elongation. Together, our experimental observations and theoretical models explain how the continuous addition of cells at the tail bud combined with lateral confinement can be converted into oriented movement and drive body elongation. © 2022. Published by The Company of Biologists Ltd

Soft Matter Models of Developing Tissues and Tumors

International audienceAnalogies with inert soft condensed matter-such as viscoelastic liquids, pastes, foams, emulsions, colloids, and polymers-can be used to investigate the mechanical response of soft biological tissues to forces. A variety of experimental techniques and biophysical models have exploited these analogies allowing the quantitative characterization of the mechanical properties of model tissues, such as surface tension, elasticity, and viscosity. The framework of soft matter has been successful in explaining a number of dynamical tissue behaviors observed in physiology and development, such as cell sorting, tissue spreading, or the escape of individual cells from a tumor. However, living tissues also exhibit active responses, such as rigidity sensing or cell pulsation, that are absent in inert soft materials. The soft matter models reviewed here have provided valuable insight in understanding morphogenesis and cancer invasion and have set bases for using tissue engineering within medicine

Rectified random cell motility as a mechanism for embryo elongation

International audienceThe body of vertebrate embryos forms by posterior elongation from a terminal growth zone called the tail bud. The tail bud is a source of highly motile cells that eventually constitute the presomitic mesoderm (PSM), a tissue that plays an important role in elongation movements. PSM cells establish an anterior-posterior cell motility gradient that parallels a gradient associated with the degradation of a specific cellular signal (FGF) known to be implicated in cell motility. Here, we combine the electroporation of fluorescent reporters in the PSM with time-lapse imaging in the chicken embryo to quantify cell diffusive movements along the motility gradient. We show that a simple microscopic model for random cell motility induced by FGF activity along with geometric confinement leads to rectified tissue elongation consistent with our observations. A continuum analog of the microscopic model leads to a macroscopic mechano-chemical model for tissue extension that couples FGF activity-induced cell motility and tissue rheology, and is consistent with the experimentally observed speed and extent of elongation. Together, our experimental observations and theoretical models explain how the continuous addition of cells at the tail bud combined with lateral confinement can be converted into oriented movement and drive body elongation

α-Hemolysin membrane pore density measured on liposomes

International audienceMembrane pore proteins are powerful tools that allow manipulation of the inside composition of micron sized bioreactors such as artificial liposomes. While the pores self-assemble very reliably on phospholipid bilayers, the determination of the number of pores in situ for liposomes remains difficult. Here we present three independent methods to establish the number of pores on different types of liposomes: (A) the loss of refractive index due to equilibration of the inside and outside buffer conditions, and the loss of volume by (B) membrane aspiration and by (C) membrane tether pulling experiments. With these three methods we are able to determine the pore density on the membrane, and all measurements give similar values; an average pore distance is found on the order of 100 nm

Mechanics of Biomimetic Liposomes Encapsulating an Actin Shell

International audienceCell-shape changes are insured by a thin, dynamic, cortical layer of cytoskeleton underneath the plasma membrane. How this thin cortical structure impacts the mechanical properties of the whole cell is not fully understood. Here, we study the mechanics of liposomes or giant unilamellar vesicles, when a biomimetic actin cortex is grown at the inner layer of the lipid membrane via actin-nucleation-promoting factors. Using a hydrodynamic tube-pulling technique, we show that tube dynamics is clearly affected by the presence of an actin shell anchored to the lipid bilayer. The same force pulls much shorter tubes in the presence of the actin shell compared to bare membranes. However, in both cases, we observe that the dynamics of tube extrusion has two distinct features characteristic of viscoelastic materials: rapid elastic elongation, followed by a slower elongation phase at a constant rate. We interpret the initial elastic regime by an increase of membrane tension due to the loss of lipids into the tube. Tube length is considerably shorter for cortex liposomes at comparable pulling forces, resulting in a higher spring constant. The presence of the actin shell seems to restrict lipid mobility, as is observed in the corral effect in cells. The viscous regime for bare liposomes corresponds to a leakout of the internal liquid at constant membrane tension. The presence of the actin shell leads to a larger friction coefficient. As the tube is pulled from a patchy surface, membrane tension increases locally, leading to a Marangoni flow of lipids. As a conclusion, the presence of an actin shell is revealed by its action that alters membrane mechanics

Spreading Dynamics of Biomimetic Actin Cortices

Reconstituted systems mimicking cells are interesting tools for understanding the details of cell behavior. Here, we use an experimental system that mimics cellular actin cortices, namely liposomes developing an actin shell close to their inner membrane, and we study their dynamics of spreading. We show that depending on the morphology of the actin shell inside the liposome, spreading dynamics is either reminiscent of a bare liposome (in the case of a sparse actin shell) or of a cell (in the case of a continuous actin shell). We use a mechanical model that qualitatively accounts for the shape of the experimental curves. From the data on spreading dynamics, we extract characteristic times that are consistent with mechanical estimates. The mechanical characterization of such stripped-down experimental systems paves the way for a more complex design closer to a cell. We report here the first step in building an artificial cell and studying its mechanics

Editorial: Viscoelasticity: From Individual Cell Behavior to Collective Tissue Remodeling

This issue gathers exciting multi-disciplinary work relating viscoelasticity and collective cell remodeling within various biological processes such as morphogenesis, tumorigenesis, and wound healing. Viscoelasticity is influenced by energy transfer and dissipation during cell rearrangement at various time and space scales. Cumulative structural changes at a subcellular level have effects on viscoelasticity at a supracellular level. Established configurations of migrating cells and the rate of their change, which significantly regulate viscoelasticity at a supracellular level, have the impact on the cohesiveness inhomogeneity and various mechanical and biochemical processes at a subcellular level. This Research Topic aims to connect the macroscopic viscoelastic parameters with the individual and collective cell response. Consideration of biochemical, biophysical and bio-mechanical aspects responsible for tissue remodeling, intercalation, and migration were discussed on various multicellular systems under in vivo and in vitro conditions. Thus in this Research Topic we aim to provide a state-of-the-art view about the current knowledge related to viscoelasticity caused by collective cell remodeling and adhesive contractile properties, covering a plethora of phenomena such as: 1) single cell response under stretched monolayers modeled with an improved Vertex model, 2) adhesion percolation within a tissue as an important factor which influences its viscoelasticity, 3) the active turbulence caused by collective cell migration accompanied with the generation of mechanical waves, 4) cell jamming state transitions, and 5) viscoelastic response characterization in liver diseases. Alternative techniques to measure and control cell rearrangement under various experimental conditions are also considered, including atomic force microscopy measurements and various elastography techniques. This Research Topic provides an overview of the current understanding of various: biological, biochemical, biophysical and mechanical aspects of cell remodeling. The inter-relation between cell remodeling and tissue viscoelasticity was discussed by emphasizing the relevant rheological parameters, the way of their measurement under in vivo/ in vitro conditions, and the strategy of multi-scale constitutive modeling