Biology subjects

Dessalles, C. A.

Publications and source records attributed to Dessalles, C. A..

3 recordsLinked to original sources

bioRxiv2023

1D confinement mimicking microvessel geometry controls pericyte shape and motility

Pericytes are mural cells of the microvasculature, characterised by their elongated distinct shape. Pericytes span along the axis of the vessels they adhere to, therefore they experience extreme lateral and longitudinal confinement. Pericyte shape is key for their function during vascular regulation and their spatial distribution is established by cell migration during the embryonic stage and maintained through controlled motility in the adult. However, how pericyte morphology is associated with migration and function remains unknown. We use micropatterns to mimic pericyte adhesion to vessels, and to reproduce in vitro the shapes adopted by pericytes in vivo. We show that lateral confinement controls cell shape and produces in vivo-like phenotype. Modelling the pericyte as an incompressible linear elastic material predicts strain and shape of pericytes as a function of lateral confinement. Pericyte kinetics on both laterally confining lanes, and longitudinally constraining motifs is described by dry friction theory. Pericytes are capable of crossing gaps of different sizes. The percentage of crossings is correctly predicted by the likelihood of a fluctuating system to overcome an energy barrier. Our joint experimental and theoretical approach demonstrates the effect of in vivo-like geometrical confinement on pericyte morphology and migration which is accurately described by dry friction theory.

biophysics↗

bioRxiv2021

The desmin mutation R349P increases contractility and fragility of stem cell-generated muscle micro-tissues

Desminopathies comprise hereditary myopathies and cardiomyopathies caused by mutations in the intermediate filament protein desmin that lead to severe and often lethal degeneration of striated muscle tissue. Animal and single cell studies hinted that this degeneration process is associated with massive ultrastructural defects correlating with increased susceptibility of the muscle to acute mechanical stress. The underlying mechanism of mechanical susceptibility, and how muscle degeneration develops over time, however, has remained elusive. Here, we investigated the effect of a desmin mutation on the formation, differentiation, and contractile function of in vitro-engineered three-dimensional micro-tissues grown from muscle stem cells (satellite cells) isolated from heterozygous R349P desmin knock-in mice. Micro-tissues grown from desmin-mutated cells exhibited spontaneous unsynchronized contractions, higher contractile forces in response to electrical stimulation, and faster force recovery compared to tissues grown from wild-type cells. Within one week of culture, the majority of R349P desmin-mutated tissues disintegrated, whereas wild-type tissues remained intact over at least three weeks. Moreover, under tetanic stimulation lasting less than five seconds, desmin-mutated tissues partially or completely ruptured, whereas wild-type tissues did not display signs of damage. Our results demonstrate that the progressive degeneration of desmin-mutated micro-tissues is closely linked to extracellular matrix fiber breakage associated with increased contractile forces and unevenly distributed tensile stress. This suggests that the age-related degeneration of skeletal and cardiac muscle in patients suffering from desminopathies may be similarly exacerbated by mechanical damage from high-intensity muscle contractions. We conclude that micro-tissues may provide a valuable tool for studying the organization of myocytes and the pathogenic mechanisms of myopathies.

biophysics↗

bioRxiv2021

Luminal Flow Actuation Generates Coupled Shear and Strain in a Microvessel-on-Chip

In the microvasculature, blood flow-derived forces are key regulators of vascular structure and function. Consequently, the development of hydrogel-based microvessel-on-chip systems that strive to mimic the in vivo cellular organization and mechanical environment has received great attention in recent years. However, despite intensive efforts, current microvessel- on-chip systems suffer from several limitations, most notably failure to produce physiologically relevant wall strain levels. In this study, a novel microvessel-on-chip based on the templating technique and using luminal flow actuation to generate physiologically relevant levels of wall shear stress and circumferential stretch is presented. Normal forces induced by the luminal pressure compress the surrounding soft collagen hydrogel, dilate the channel, and create large circumferential strain. The fluid pressure gradient in the system drives flow forward and generates realistic pulsatile wall shear stresses. Rigorous characterization of the system reveals the crucial role played by the poroelastic behavior of the hydrogel in determining the magnitudes of the wall shear stress and strain. The experimental measurements are combined with an analytical model of flow in both the lumen and the porous hydrogel to provide an exceptionally versatile user manual for an application-based choice of parameters in microvessels-on-chip. This unique strategy of flow actuation adds a dimension to the capabilities of microvessel-on-chip systems and provides a more general framework for improving hydrogel-based in vitro engineered platforms. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/439271v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1a4fed5org.highwire.dtl.DTLVardef@15680f4org.highwire.dtl.DTLVardef@2c2a6dorg.highwire.dtl.DTLVardef@1955f52_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗