publications
my publications in reversed chronological order
2023
- Mechanics of epithelial tissue subjected to controlled pressureNimesh R. Chahare2023
Epithelial sheets form specialized 3D structures suited to their physiological roles, such as branched alveoli in the lungs, tubes in the kidney, and villi in the intestine. To generate and maintain these structures, epithelia must undergo complex 3D deformations across length and time scales. How epithelial shape arises from active stresses, viscoelasticity, and luminal pressure remains poorly understood. To address this question, we developed a microfuidic chip and a computational framework to engineer 3D epithelial tissues with controlled shape and pressure. In the setup, an epithelial monolayer is grown on a porous surface with circular low adhesion zones. On applying hydrostatic pressure, the monolayer delaminates into a spherical cap from the circular zone. This simple shape allows us to calculate epithelial tension using Laplace’s law. Through this approach, we subject the monolayer to a range of lumen pressures at different rates and hence probe the relation between strain and tension in different regimes while computationally tracking actin dynamics and their mechanical effect at the tissue scale. Slow pressure changes relative to the actin dynamics allow the tissue to accommodate large strain variations. However, under sudden pressure reductions, the tissue develops buckling patterns and folds with different degrees of symmetry-breaking to store excess tissue area. These insights allow us to pattern epithelial folds through rationally directed buckling. Our study establishes a new approach for engineering epithelial morphogenetic events
2022
- Mechanical force application to the nucleus regulates nucleocytoplasmic transportIon Andreu, Ignasi Granero-Moya, Nimesh R. Chahare, Kessem Clein, and 7 more authorsNature Cell Biology 2022
Mechanical force controls fundamental cellular processes in health and disease, and increasing evidence shows that the nucleus both experiences and senses applied forces. Such forces can lead to the nuclear translocation of proteins, but whether force controls nucleocytoplasmic transport, and how, remains unknown. Here we show that nuclear forces differentially control passive and facilitated nucleocytoplasmic transport, setting the rules for the mechanosensitivity of shuttling proteins. We demonstrate that nuclear force increases permeability across nuclear pore complexes, with a dependence on molecular weight that is stronger for passive than for facilitated diffusion. Owing to this differential effect, force leads to the translocation of cargoes into or out of the nucleus within a given range of molecular weight and affinity for nuclear transport receptors. Further, we show that the mechanosensitivity of several transcriptional regulators can be both explained by this mechanism and engineered exogenously by introducing appropriate nuclear localization signals. Our work unveils a mechanism of mechanically induced signalling, probably operating in parallel with others, with potential applicability across signalling pathways.
2021
- The force loading rate drives cell mechanosensing through both reinforcement and cytoskeletal softeningIon Andreu, Bryan Falcones, Sebastian Hurst, Nimesh R. Chahare, and 7 more authorsNature communications 2021
Cell response to force regulates essential processes in health and disease. However, the fundamental mechanical variables that cells sense and respond to remain unclear. Here we show that the rate of force application (loading rate) drives mechanosensing, as predicted by a molecular clutch model. By applying dynamic force regimes to cells through substrate stretching, optical tweezers, and atomic force microscopy, we find that increasing loading rates trigger talin-dependent mechanosensing, leading to adhesion growth and reinforcement, and YAP nuclear localization. However, above a given threshold the actin cytoskeleton softens, decreasing loading rates and preventing reinforcement. By stretching rat lungs in vivo, we show that a similar phenomenon may occur. Our results show that cell sensing of external forces and of passive mechanical parameters (like tissue stiffness) can be understood through the same mechanisms, driven by the properties under force of the mechanosensing molecules involved.
- Role of fiber orientations in the mechanics of bioinspired fiber-reinforced elastomersAritra Chatterjee, Nimesh R. Chahare, Paturu Kondaiah, and Namrata GundiahSoft Robotics 2021
Fiber reinforcement is a crucial attribute of soft-bodied muscular hydrostats that have the ability to undergo large deformations and maintain their posture. Helically wound fibers around the cylindrical worm body help control the tube diameter and length. Geometric considerations show that a fiber winding angle of 54.7°, called the magic angle, results in a maximum enclosed volume. Few studies have combined both experimental and theoretical techniques to explore the effects of fiber winding at varied angles on the large deformation mechanics of fiber-reinforced elastomers (FRE). We fabricated FRE materials in transversely isotropic layouts varying from 0° to 90° using a custom filament winding technique and characterized the nonlinear stress–strain relationships using uniaxial and equibiaxial experiments. We used these data within a continuum mechanical framework to propose a novel constitutive model for incompressible FRE materials with embedded extensible fibers. The model includes individual contributions from the matrix and fibers in addition to coupled terms in strain invariants, I1 and I4. The deviatoric stress components show inversion at fiber orientation angles near the magic angle in the FRE composites. These results are useful in soft robotic applications and in the biomechanics of fiber-reinforced tissues such as the myocardium, arteries, and skin.
2020
- Cutting mechanics of wood by beetle larval mandiblesLakshminath Kundanati, Nimesh R. Chahare, Siddhartha Jaddivada, Abhijith G Karkisaval, and 3 more authorsJournal of the Mechanical Behavior of Biomedical Materials 2020
Wood boring is a feature of several insect species and is a major cause of severe and irreparable damage to trees. Adult females typically deposit their eggs on the stem surface under bark scales. The emerging hatchlings live within wood during their larval phase, avoiding possible predation, whilst continually boring and tunneling through wood until pupation. A study of wood boring by insects offers unique insights into the bioengineering principles that drive evolutionary adaptations. We show that larval mandibles of the coffee wood stem borer beetle (Xylotrechus quadripes: Cerambycidae) have a highly sharp cusp edge to initiate fractures in Arabica wood and a suitable shape to generate small wood chips that are suitable for digestion. Cuticle hardness at the tip is significantly enhanced through zinc-enrichment. A hollow architecture significantly reduces bending stresses at the mandibular base without compromising the structural integrity. Finite element model of the mandible showed highest stresses in the tip region; these decreased to significantly lower values at the start of the hollow section. A scaling model based on a fracture mechanics framework shows the importance of the mandible shape in generating optimal chip sizes. These findings contain general principles in tool design and put in focus interactions of insects and their woody hosts.
2018
2016
2014
- Design and fabrication of Hirda cracking machineNimesh R. Chahare, Vipul Satone, and Pradeep Kumar Bodige2014