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Munoz, J. J.

Publications and source records attributed to Munoz, J. J..

6 recordsLinked to original sources

Why is the purse string not enough?

Wound repair is an important mechanism to preserve tissue integrity in organisms after injury. However, why different tissues exhibit different mechanisms to repair wounds is a long-standing question that remains unanswered. In this work, we theoretically explore the role of the purse string, an actomyosin contractile cable used by tissues to close small wounds. Does the tissue 3D geometry influence the efficiency of the purse string in driving wound closure? Using a 3D biophysical model, we study in silico tissues with the same cell volumes but different aspect ratios, ranging from squamous to thick and tall tissues. The model predicts that taller cells are easily deformed by the purse string. In contrast, very squamous cells require a very strong purse string that might demand additional cellular mechanisms to close the gap. These findings establish a theoretical framework to predict the optimal biophysical mechanisms of wound healing in different tissues. Graphical abstractCells of different aspect ratios can be observed in a range of organisms with different function and mechanics. The wound healing efficiency of the purse string increases with the cell aspect ratio in our theoretical exploration. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/743165v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@874e22org.highwire.dtl.DTLVardef@11aabe3org.highwire.dtl.DTLVardef@af5e3org.highwire.dtl.DTLVardef@195197d_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

Neural sensing of surface traction modulates proprioceptive activity and locomotion in Caenorhabditis elegans

Locomotion -- whether walking, running, or crawling -- depends on the precise coordination of forces between the body and its surroundings. Two critical factors in this process are the force that resists the relative motion between two bodies, and mechanosensation, the bodys ability to sense and respond to mechanical forces. Together, they allow organisms to move efficiently, adapt to varying environments, and maintain balance. Here we show that the gentle touch receptor neurons (TRNs) in the Caenorhabditis elegans body wall are sensitive to dynamic surface traction. Using a combination of calcium recordings and traction force microscopy in freely moving animals, microfluidics, and whole connectome computer simulations, we show that MEC-4 DEG/ENaC ion channel activity depends on the crawling velocity and friction force. Mutations disrupting MEC-4 activity and body wall mechanoreceptor function produce lethargic worms with impaired proprioceptive regulation, suggesting functional coupling between surface mechanoreceptors and proprioceptors. Our data reveal a new role for classical touch receptors in locomotion and critically define the mechanical modality sensed by skin mechanosensors.

neuroscience↗

Turing pattern prediction in three-dimensional domains: the role of initial conditions and growth

Reaction-diffusion systems have been widely used to model pattern formation in biological systems. However, the emergence of Turing patterns in three-dimensional (3D) domains remains relatively unexplored. A few studies on this topic have shown that extending pattern formation from 2D to 3D is not straightforward. Linear stability analysis, which is commonly used to associate admissible wave modes with predicted patterns in 1D and 2D, has yet to be applied in 3D. We have used this approach, together with finite element modelling of a Turing system with Schnakenberg kinetics, to investigate the effects of initial conditions and growing domains on the competition between admissible modes in 3D Turing pattern emergence. Our results reveal that non-random initial conditions on the activator play a stronger role than those of the inhibitor. We also observe a path dependency of the evolving pattern within a growing domain. Our findings shed new light on the mechanisms ensuring reliable pattern formation in 3D domains and have important implications for the development of more robust models of morphogen patterning in developmental processes.

developmental biology↗

Local mechanical stimuli shape tissue growth in vertebrate joint morphogenesis

The correct formation of synovial joints is essential for proper motion throughout life. Movement-induced forces are critical to creating correctly shaped joints, but it is unclear how cells sense and respond to these mechanical cues. To determine how mechanical stimuli drive joint morphogenesis, we combined experiments on regenerating axolotl (Ambystoma mexicanum) forelimbs with a poroelastic model of bone rudiment growth. Animals either regrew forelimbs normally (control) or were injected with a TRPV4 agonist to impair chondrocyte mechanosensitivity during joint morphogenesis. We quantified growth and shape in regrown humeri from whole mount light sheet fluorescence images of the regenerated limbs. Results revealed statistically significant differences in morphology and cell proliferation between groups, indicating that mechanical stimuli play a role in the shaping of joints. We simulated local tissue growth in a finite element model with a biological contribution to growth proportional to chondrocyte density, and a mechanical contribution to growth proportional to fluid pressure. Computational predictions agreed with experimental outcomes, suggesting that interstitial pressure driven from cyclic mechanical stimuli promotes local tissue growth. Predictive computational models informed by experimental findings allow us to explore potential physical mechanisms involved in tissue growth to advance our understanding of the mechanobiology of joint morphogenesis.

developmental biology↗

Planar differential growth rates determine the position of folds in complex epithelia

Folding is a fundamental process shaping epithelial sheets into 3D architectures of organs. Initial positioning of folds is the foundation for the emergence of correct tissue morphology. Mechanisms forming individual folds have been studied, yet the precise positioning of the folds in complex, multi-folded epithelia is an open question. We present a model of morphogenesis, encompassing local differential growth, and tissue mechanics to investigate tissue fold positioning. We use Drosophila melanogaster wing imaginal disc as our model system, and show that there is spatial and temporal heterogeneity in its planar growth rates. This planar differential growth is the main driver for positioning the folds. Increased stiffness of the apical layer and confinement by the basement membrane drive fold formation. These influence fold positions to a lesser degree. The model successfully predicts the emergent morphology of wingless spade mutant in vivo, via perturbations solely on planar differential growth rates in silico.

biophysics↗

Stress relaxation in epithelial monolayers is controlled by actomyosin

Epithelial monolayers are one-cell thick tissue sheets that separate internal and external environments. As part of their function, they withstand extrinsic mechanical stresses applied at high strain rate. However, little is known about how monolayers respond to mechanical deformations. In stress relaxation tests, monolayers respond in a biphasic manner and stress dissipation is accompanied by an increase in monolayer resting length, pointing to active remodelling of cell architecture during relaxation. Consistent with this, actomyosin remodels at a rate commensurate with mechanical relaxation and governs the rate of monolayer stress relaxation - as in single cells. By contrast, junctional complexes and intermediate filaments form stable connections between cells, enabling monolayers to behave rheologically as single cells. Together, these data show actomyosin cytoskeletal dynamics govern the rheological properties of monolayers by enabling active, ATP-dependent changes in the resting length. These findings have far-reaching consequences for our understanding of developmental morphogenesis and tissue response to mechanical stress.

biophysics↗