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Biology subjects

Pinaud, F.

Publications and source records attributed to Pinaud, F..

3 recordsLinked to original sources

Single molecule tracking of bacterial cell surface cytochromes reveals dynamics that impact long-distance electron transport

Using a series of multiheme cytochromes, the metal-reducing bacterium Shewanella oneidensis MR-1 can perform extracellular electron transfer (EET) to respire redox-active surfaces, including minerals and electrodes outside the cell. While the role of multiheme cytochromes in transporting electrons across the cell wall is well established, these cytochromes were also recently found to facilitate long-distance (micrometer-scale) redox conduction along outer membranes and across multiple cells bridging electrodes. Recent studies proposed that long-distance conduction arises from the interplay of electron hopping and cytochrome diffusion, which allows collisions and electron exchange between cytochromes along membranes. However, the diffusive dynamics of the multiheme cytochromes have never been observed or quantified in vivo, making it difficult to assess their hypothesized contribution to the collision-exchange mechanism. Here we use quantum dot labeling, total internal reflection fluorescence microscopy, and single-particle tracking to quantify the lateral diffusive dynamics of the outer membrane-associated decaheme cytochromes MtrC and OmcA, two key components of EET in S. oneidensis. We observe confined diffusion behavior for both quantum dot-labeled MtrC and OmcA along cell surfaces (diffusion coefficients DMtrC = 0.0192 {+/-} 0.0018 m2/s, DOmcA = 0.0125 {+/-} 0.0024 m2/s) and the membrane extensions thought to function as bacterial nanowires. We find that these dynamics can trace a path for electron transport via overlap of cytochrome trajectories, consistent with the long-distance conduction mechanism. The measured dynamics inform kinetic Monte Carlo simulations that combine direct electron hopping and redox molecule diffusion, revealing significant electron transport rates along cells and membrane nanowires. SignificanceMultiheme cytochromes in Shewanella oneidensis MR-1 transport electrons across the cell wall, in a process called extracellular electron transfer. These electron conduits can also enable electron transport along and between cells. While the underlying mechanism is thought to involve a combination of electron hopping and lateral diffusion of cytochromes along membranes, these diffusive dynamics have never been observed in vivo. Here, we observe the mobility of quantum dot-labeled cytochromes on living cell surfaces and membrane nanowires, quantify their diffusion with single-particle tracking techniques, and simulate the contribution of these dynamics to electron transport. This work reveals the impact of redox molecule dynamics on bacterial electron transport, with implications for understanding and harnessing this process in the environment and bioelectronics.

microbiology↗

Emerin oligomerization and nucleoskeletal coupling at the nuclear envelope regulate nuclear mechanics against stress

Emerin is an integral nuclear envelope protein participating in the maintenance of nuclear shape. When mutated or absent, emerin causes X-linked Emery-Dreifuss muscular dystrophy (EDMD). To define how emerin takes parts in molecular scaffolding at the nuclear envelope and helps protect the nucleus against mechanical stress, we established its nanoscale organization using single molecule tracking and super-resolution microscopy. We show that emerin monomers form localized oligomeric nanoclusters stabilized by both lamin A/C and SUN1 at the LINC complex. Interactions of emerin with nuclear actin and BAF additionally modulate its membrane mobility and its ability to oligomerize. In nuclei subjected to mechanical challenges, the mechanotransducing functions of emerin are coupled to changes in its oligomeric state, and the incremental self-assembly of emerin determines nuclear shape adaptation against forces. We also show that the abnormal nuclear envelope deformations induced by EDMD emerin mutants stem from an improper formation of lamin A/C and LINC complex-stabilized emerin oligomers. These findings place emerin at the center of the molecular processes that regulate nuclear shape remodeling in response to mechanical challenges.

cell biology↗

Focused ultrasound stimulates ER localized mechanosensitive PANNEXIN-1 to mediate intracellular calcium release in invasive cancer cells

Focused ultrasound (FUS) is a rapidly developing stimulus technology with the potential to uncover novel mechanosensory dependent cellular processes. Since it is noninvasive, it holds great promise for future therapeutic applications in patients used either alone or as a complement to boost existing treatments. For example, FUS stimulation causes invasive but not noninvasive cancer cell lines to exhibit marked activation of calcium signaling pathways. Here, we identify the membrane channel PANNEXIN1 (PANX1) as a mediator for activation of calcium signaling in invasive cancer cells. Knockdown of PANX1 decreases calcium signaling in invasive cells, while PANX1 overexpression enhances calcium elevations in non-invasive cancer cells. We demonstrate that FUS may directly stimulate mechanosensory PANX1 localized in endoplasmic reticulum to evoke calcium release from internal stores. This process does not depend on mechanosensory stimulus transduction through an intact cytoskeleton and does not depend on plasma membrane localized PANX1. Plasma membrane localized PANX1 however plays a different role in mediating the spread of intercellular calcium waves via ATP release. Additionally, we show that FUS stimulation evokes cytokine/chemokine release from invasive cancer cells, suggesting that FUS could be an important new adjuvant treatment to improve cancer immunotherapy.

cell biology↗