Search bioRxiv⌕ Search

Biology subjects

Cetiner, U.

Publications and source records attributed to Cetiner, U..

4 recordsLinked to original sources

Dissipation During the Gating Cycle of the Bacterial Mechanosensitive Ion Channel Approaches the Landauer's Limit

The Landauers principle sets a thermodynamic bound of kBT ln 2 on the energetic cost of erasing each bit of information. It holds for any memory device, regardless of its physical implementation. It was recently shown that carefully built artificial devices can saturate this bound. In contrast, biological computation-like processes, e.g., DNA replication, transcription and translation use an order of magnitude more than their Landauers minimum. Here we show that saturating the Landauer bound is nevertheless possible with biological devices. This is done using a mechanosensitive channel of small conductance (MscS) from E. coli as a memory bit. MscS is a fast-acting osmolyte release valve adjusting turgor pressure inside the cell. Our patch-clamp experiments and data analysis demonstrate that under a slow switching regime, the heat dissipation in the course of tension-driven gating transitions in MscS closely approaches its Landauers limit. We discuss the biological implications of this physical trait.

biophysics↗

A bacterial-like mechanosensitive channel controls osmoregulation and infectivity in Trypanosoma cruzi

Trypanosoma cruzi, the causative agent of Chagas disease, undergoes drastic morphological and biochemical modifications as it passes between hosts and transitions from extracellular to intracellular stages. The osmotic and mechanical aspects of these cellular transformations are not understood. Here we identify and characterize a novel mechanosensitive channel in T. cruzi (TcMscS) belonging to the superfamily of small conductance mechanosensitive channels (MscS). TcMscS is activated by membrane tension and forms a large pore permeable to anions, cations, and small osmolytes. The channel changes its location from the contractile vacuole complex in epimastigotes to the plasma membrane as the parasites develop into intracellular amastigotes. TcMscS knockout parasites show significant fitness defects, including increased cell volume, calcium dysregulation, impaired differentiation, and a dramatic decrease in infectivity. Our work provides mechanistic insights into components supporting pathogen adaptation inside the host thus opening the exploration of mechanosensation as a prerequisite of protozoan infectivity.

microbiology↗

Recovery of equilibrium free energy from non-equilibrium thermodynamics with mechanosensitive ion channels in E. coli

Bacterial mechanosensitive channels are major players in cells ability to cope with hypo-osmotic stress. Excess turgor pressure due to fast water influx is reduced as the channels, triggered by membrane tension, open and release osmolytes. However, in vitro measurements of the free energy difference between the open and closed states of ion channels are challenging due to hysteresis effects and inactivation. Exploiting recent developments in statistical physics, we present a general formalism to extract the free energy difference between the closed and open states of mechanosensitive ion channels from non-equilibrium work distributions associated with the channels gating recorded in native patches under ramp stimulation protocols. We show that the work distributions obtained from the gating of MscS channels in E. coli membrane satisfy the strong symmetry relations predicted by the fluctuation theorems and recover the equilibrium free energy difference between the closed and open states of the channel within 1 kB T of its best estimate obtained from an independent experiment.

biophysics↗

Spatiotemporal relationships defining the adaptive gating of the bacterial mechanosensitive channel MscS

Adaptive desensitization and inactivation are common properties of most ion channels and receptors. The mechanosensitive channel of small conductance MscS, which serves as a low-threshold osmolyte release valve in most bacteria, is unusual because it slowly inactivates not from the open, but from the resting state under moderate tensions. The manifestation of this mechanism is the channels ability to discriminate the rate of tension application, i.e., to ignore slow tension ramps but fully respond to abruptly applied stimuli. In this work, we present a reconstruction of the landscape for tension-dependent MscS transitions based on patch current kinetics recorded under specially designed pressure protocols. The data are analyzed with a three-state continuous time Markov model of gating, where the tension-dependent transition rates are governed by Arrhenius-type relations. The analysis provides assignments to the intrinsic opening, closing, inactivation, and recovery rates as well as their tension dependencies. These parameters, which define the spatial (areal) distances between the energy wells and the positions of barriers, describe the tension-dependent distribution of the channel population between the three states and quantitatively predict the experimentally observed dynamic pulse and ramp responses. Our solution also provides an analytic expression for the area of the inactivated state in terms of two experimentally accessible parameters: the tension at which inactivation probability is maximized, {gamma}*, and the midpoint tension for activation, {gamma}0.5. The analysis initially performed on Escherichia coli MscS shows its applicability to the previously uncharacterized MscS homolog from Pseudomonas aeruginosa. MscS inactivation minimizes metabolic losses during osmotic permeability response and thus contributes to the environmental fitness of bacteria.

biophysics↗