A biomimetic approach to mechanosensitive tactile perception
Internship title: A biomimetic approach to mechanosensitive tactile perception
Name: Jean Perrin Laboratory
Affiliation: UMR 8237 CNRS – Sorbonne Université
Address: 4 place Jussieu,
Name: Georges Debrégeas
Phone number: 0144274714
Name: Elie Wandersman
Phone number: 0144272823
Subject Keywords: mechanosensitivity, vesicles, pores,
Tools and methodologies: fluorescence microscopy
Summary of lab\’s interests: All the activities of the LJP come within physics at the interface with biology and medicine. A large part of our research projects aims at exploring the response of a biological system to external perturbations.
On the one hand, we search for realizing new physico-chemical, mechanical systems the behaviours of which could offer some analogies with the biological systems — an approach that we could qualify of bio-inspired, allowing to go back and forth from the alive to the artificial systems, either to develop new concepts or to improve our understanding of given biological mechanisms by trying to reproduce them artificially. In line with this, we are developing projects which concern the solid friction in relation with the mechanics of the sense of touch or membrane biophysics in relation with intracellular traffic issues.
On the other hand, we have a significant interest in developing new experimental approaches, in particular in the field of optics and microfabrication techniques with a special attention to techniques from microelectronics field enabling manufacturing of microstructures (mainly passive, but which could also turn to MEMS’s active microstructures), the characteristic sizes of which go from the micron to a few hundred microns. These approaches allow us to probe the properties of complex biological systems at different scales. This includes researches on zebra neurobiology and on microorganisms examined from the single cell to the organized community scale.
Eventually, we decided from the very beginning of Laboratoire Jean Perrin creation, to include a theoretical component to our researches. This is crucial both for scientific animation and for supporting experimenter modelling activities. Theoreticians of the lab develop new concepts based on the daily interaction with the experimenters.
Project summary: Humans detect the shape and texture of an object through direct contact (static and / or dynamic) between the tactile organ (usually the tip of the finger) and the surface of the object. This contact induces deformations and vibrations of the surface of the skin which are measured by subcutaneous mechanosensitive nerve cells, that are called mechanoreceptors. These cells transform the mechanical stress signal into action potentials that are directly interpreted by the central nervous system. On a microscopic scale, the mechanosensitivity of these cells is due to the presence of mechanosensitive protein pores embedded in their membrane that open and let the ions flow under mechanical stress. This results in transmembrane ion fluxes that modify the ionic permeability of the membrane and depolarize it, which ultimately triggers an action potential.
During this internship, and in the longer term for this thesis project, we will adopt a biomimetic approach to mimick the subcutaneous tactile mechanoreceptors and measure their response under mechanical stress. To do this, we will trap giant lipid vesicles in agarose gel (the skin analog), whose membrane will be decorated with mechanosensitive protein pores (the analogue of a mechanoreceptor). These vesicles trapped in agar are already routinely produced in the laboratory thanks to an easy-to-use microfluidic method that we have recently developed . We will use the mechanosensitive MscL pore found on the outer membrane of E. Coli bacteria. These will be obtained with synthetic biology methods mastered in the team . We will probe the properties of ion transport across the membrane when the agar gel is mechanically excited, with controlled amplitude and frequency. The vesicle will contain calcium ions and we will set up a calcium imaging device to track the leakage of ions through the membrane under mechanical stress. We will establish how the amplitude and frequency of mechanical excitation, as well as the viscoelastic properties of the gel, modulate the ion transport across the membrane.
 S. S. Ranade et al., Neuron 87, 1162 (2015)
 M.Valet et al. Phys. Rev. Applied 9 (1) 014002 (2018) & M. Valet et al. Phys. Rev. Lett. 123, 088101 (2019)
 M. Valet, Thèse de Doctorat, Sorbonne Université, Septembre 2019.
Interdisciplinary aspect of the project: This project combines different concepts and techniques to unravel the response of mechanosensitive cells in a simplified framework. On the biological front it requires the use of powerful cell-free protein expression techniques for the synthesis of mechanosensitive pores. Indeed, such amphiphilic proteins need to be expressed near a membrane in order to fold properly. In liposomes this toolbox will thus open to path to the synthesis of a wide range of complex membrane proteins that are otherwise inaccessible through classical purification techniques. The project also has a strong soft matter component through the synthesis of liposomes thanks to a novel microfluidics technique that was developed in our group. Finally, there is also a theoretical aspect to the description of molecular leakage through discrete stress-dependant pores on the surface of the vesicle.