The filamentous temperature-sensitive (Fts) protein FtsEX plays a pivotal role in Escherichia coli ( E. coli ) cell division by facilitating the activation of peptidoglycan hydrolysis through the adaptor EnvC. FtsEX belongs to the type VII ATP-binding cassette (ABC) transporter superfamily, which harnesses ATP energy to induce mechanical force, triggering a cascade of conformational changes that activate the pathway. However, the precise mechanism by which FtsEX initiates mechanotransmission remains elusive. Due to the inherent instability of this type of ABC transporter protein in vitro, the conformation of FtsEX has solely been determined in the stabilized ATP-bound state. To elucidate the dynamics of FtsEX, we characterized FtsEX and EnvC of various functional structures through cryo-electron microscopy (cryo-EM) and homology modeling. We validated the structures by molecular dynamics simulations. By site-directed mutagenesis and phenotype screening, we also identified the functional residues involved in allosteric communication between FtsE and FtsX as well as FtsX and EnvC. Additionally, we discovered a potential role of phospholipids in stabilizing the complex conformation during mechanotransmission. This comprehensive exploration significantly enhances our understanding of the intricate mechanisms governing bacterial cell division and unveils potential molecular targets for developing innovative antimicrobial drugs to combat antibiotic resistance.
Hydrogen peroxide (H2O2) levels play a vital role in redox regulation and maintaining the physiological balance of living cells, especially in cell mechanotransduction. Despite the achievements on strain-induced cellular H2O2 monitoring, the applied voltage for H2O2 electrooxidation possibly gave rise to an abnormal expression and inadequate accuracy, which was still an inescapable concern. Hence, we decorated an interlaced CuO@TiO2 nanowires (NWs) semiconductor meshwork onto a polydimethylsiloxane film-supported gold nanotubes substrate (Au NTs/PDMS) to construct a flexible photoelectrochemical (PEC) sensing platform. Under white light irradiation, CuO@TiO2 NWs synergistically exhibited great stretchability and the PEC platform enabled stable photocurrent responses from the reduction of H2O2 even during mechanical deformation. Moreover, the admirable biocompatibility and an almost negligible open circuit voltage of +0.18 V for the CuO@TiO2 NWs/Au NTs/PDMS sensor guaranteed human umbilical vein endothelial cells (HUVECs) adhesion tightly thereon even under continuous illumination for 30 min. Finally, the as-proposed stretchable PEC sensor achieved sensitive and true-to-life monitoring of transient H2O2 release during HUVECs deformation, in which H2O2 release was positively correlated to mechanical strains. This investigation opens a new shade path on in situ cellular sensing and meanwhile greatly expands the application mode of the PEC approach.
As the early step of food ingestion, the swallow is under rigorous sensorimotor control. Nevertheless, the mechanisms underlying swallow control at a molecular and circuitry level remain largely unknown. Here, we find that mutation of the mechanotransduction channel genes nompC, Tmc, or piezo impairs the regular pumping rhythm of the cibarium during feeding of the fruit fly Drosophila melanogaster. A group of multi-dendritic mechanosensory neurons, which co-express the three channels, wrap the cibarium and are crucial for coordinating the filling and emptying of the cibarium. Inhibition of them causes difficulty in food emptying in the cibarium, while their activation leads to difficulty in cibarium filling. Synaptic and functional connections are detected between the pharyngeal mechanosensory neurons and the motor circuit that controls swallow. This study elucidates the role of mechanosensation in swallow, and provides insights for a better understanding of the neural basis of food swallow.
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