Biology subjects

Parthasarathi, S.

Publications and source records attributed to Parthasarathi, S..

3 recordsLinked to original sources

bioRxiv2026

Stearic acid enhances membrane fluidization and peptidoglycan stiffness to promote the stability of Gram-positive bacteria

Saturated fatty acids such as stearic acid (SA) can exhibit both antimicrobial and growth-promoting effects on bacteria, depending on their concentration and chemical structure. However, the physical properties of the bacterial cell envelope in response to such molecules remain under-explored compared to their biochemical pathways. In this study, a comprehensive investigation is presented on the interaction of SA with the Gram-positive bacterium, Staphylococcus epider-midis (S. epi). SA alters bacterial growth, reflected in a higher maximum specific growth rate, a shorter lag phase, and an extended exponential phase, consistent with a prebiotic effect. Using fluorescence correlation spectroscopy and fluorescence lifetime imaging microscopy, we show that SA incorporation leads to significant fluidization of the lipid membrane, characterized by enhanced lateral diffusion and reduced membrane viscosity. Coarse-grained molecular dynamics (CG-MD) simulations demonstrate spontaneous insertion of SA into the membrane and a significant increase in mean-square displacement after insertion, supporting our experimental observations. Importantly, atomic force microscopy measurements show an increase in cell-envelope stiffness, reflected by a higher Youngs modulus which can be attributed to modulations in the glycan-peptide linkage density based on earlier studies that correlate stiffness changes to peptidoglycan (PG) crosslinking in Gram-positive strains [1]. These results provide direct evidence linking membrane fluidization induced by SA and increased cell wall stiffness due to transport modifications in the membrane mediated PG synthesis pathways to enhance bacterial cell viability.

biophysics↗

bioRxiv2024

Structural and functional insights into nuclear role of Parkinson's Disease-associated α-Synuclein

-Synuclein (Syn) plays a critical role in the pathogenesis of Synucleinopathies. Although increased nuclear Syn localization induces neurotoxicity, its definitive physiological role remains elusive. Previous studies on nuclear Syn are limited to its interactions with individual histones and dsDNA, leaving a significant gap in understanding its interactions with assembled histone H2a-H2b dimer and (H3-H4)2 tetramer, as well as its role in chromatin regulation. Here, we demonstrated that Syn binds specifically to both H2a-H2b and (H3-H4)2 with high affinity. Truncation studies revealed that Syn(1-103) region interacts with (H3-H4)2, while the acidic (121-140) C-terminal end is crucial for H2a-H2b binding. Sequence analysis suggests Syn-dimer binding region contains a conserved DEF/YxP motif present in other dimer-binding histone chaperones. High-resolution structure of Syn- dimer binding region with H2a-H2b complex reveals that Syn adopts two binding modes (BM1 and BM2). In BM-1, Syn utilizes nucleosomal DNA-binding surface, while in BM-2, it engages with both DNA- and the H3-interaction interface. Additionally, dimer recognition by Syn overlaps with other dimer-binding histone chaperones, suggesting Syns potential role in the nucleosome assembly/disassembly process.

biophysics↗

bioRxiv2021

Interactions of surfactants with the bacterial cell wall and inner membrane: Revealing the link between aggregation and antimicrobial activity

Surfactants with their intrinsic ability to solubilize lipids are widely used as antibacterial agents. Interaction of surfactants with the bacterial cell envelope is complicated due to their propensity to aggregate. It is important to discern the interactions of micellar aggregates and single surfactants on the various components of the cell envelope to improve selectivity and augment the efficacy of surfactant-based products. In this study, we present a combined experimental and molecular dynamics investigation to unravel the molecular basis for the superior kill efficacy of laurate over oleate observed in contact time assays with live E. coli. To gain a molecular understanding of these differences, we performed all-atom molecular dynamics simulations to observe the interactions of surfactants with the periplasmic peptidoglycan layer and the inner membrane of Gram-negative bacteria. The peptidoglycan layer allows a greater number of translocation events for laurate when compared with oleate molecules. More interestingly, aggregates did not translocate the peptidoglycan layer, thereby revealing an intrinsic sieving property of the bacterial cell wall to effectively modulate the surfactant concentration at the inner membrane. The molecular dynamics simulations exhibit greater thinning of the inner membrane in the presence of laurate when compared with oleate, and laurate induced greater disorder and decreased the bending modulus of the inner membrane to a greater extent. The enhanced antimicrobial efficacy of laurate over oleate was further verified by experiments with giant unilamellar vesicles, which revealed that laurate induced vesicle rupture at lower concentrations in contrast to oleate. The novel molecular insights gained from our study uncovers hitherto unexplored pathways to rationalize the development of antimicrobial formulations and therapeutics.

biophysics↗