Biology subjects

Rani, G.

Publications and source records attributed to Rani, G..

5 recordsLinked to original sources

bioRxiv2023

Activity-driven emergence of genealogical enclaves in growing bacterial colonies

Bacterial dispersal, the movement of cells spanning diverse physical scales and environments, has been long investigated owing to its far-reaching ramifications in the ecology and evolution of bacterial species and their consortia. A major proportion of bacterial species are surface associated, yet if and how they disperse, specifically during the early stages of biofilm formation, remains to be understood. While physical vectors like fluid flow drive dispersal across large scales, surface-associated cells may benefit from the active biomechanical forces to navigate locally within a colony. Here, by analyzing sessile bacterial colonies, we study how cells disperse over generations due to the growth-induced forces under different conditions. A custom-built labelfree algorithm, developed to track the progeny cells as they grow and divide, reveals the emergence of distinct self-similar genealogical enclaves which intermix over time. Biological activity, indicated by the division times, is a key determinant of the intermixing dynamics; while topological defects appearing at the interface of the enclaves mediate the morphology of finger-like interfacial domains. By quantifying the Shannon entropy, we show that dividing bacterial cells have spatial affinity to close relatives, at the cost of the entropically favourable option of intermixing, wherein faster growing colonies show higher drop in the Shannon entropy over time. A coarse-grained lattice modelling of such colonies, combined with insights from the thermodynamics of phase separation, suggest that the emergence of genealogical enclaves results from an interplay of growth-induced cell dispersal within the colony (which promotes intermixing) and stochasticity of cell division, alongwith the cell-cell interactions at a given growth condition. Our study uncovers the evolution of so-far hidden emergent self-organising features within growing bacterial colonies, which while displaying a high degree of self-similarity on a range of phenotypic traits, point at competing roles of growth-induced forces and entropic landscapes which ultimately shape the genealogical distance of cells to their kith and kin within growing colonies. One Sentence SummaryLabel-free tracking of cells reveals spatio-temporal evolution of genealogical enclaves in growing bacterial colonies resulting from activity-controlled emergent demixing of cell lineages.

biophysics↗

bioRxiv2022

Role of lipid packing defects in determining membraneinteractions of antimicrobial polymers

Understanding the emergence and role of lipid packing defects in the detection and subsequent partitioning of antimicrobial agents into bacterial membranes is essential for gaining insights into general antimicrobial mechanisms. Herein, using methacrylate polymers as a model platform, we investigate the effects of inclusion of various functional groups in the biomimetic antimicrobial polymer design on the aspects of lipid packing defects in model bacterial membranes. Two antimicrobial polymers are considered: ternary polymers composed of cationic, hydrophobic and polar moieties and binary polymers with only cationic and hydrophobic moieties. We find that differing modes of insertion of these two polymers lead to different packing defects in the bacterial membrane. While insertion of both binary and ternary polymers leads to an enhanced number of deep defects in the upper leaflet, shallow defects are moderately enhanced upon interaction with ternary polymers only. We provide conclusive evidence that insertion of antimicrobial polymers in bacterial membrane is preceded by sensing of interfacial lipid packing defects. Our simulation results show that the hydrophobic groups are inserted at a single co-localized deep defect site for both binary and ternary polymers. However, the presence of polar groups in the ternary polymers use the shallow defects close to the lipid-water interface, in addition, to insert into the membrane, which leads to a more folded conformation of the ternary polymer in the membrane environment, and hence a different membrane partitioning mechanism compared to the binary polymer, which acquires an amphiphilic conformation.

biophysics↗

bioRxiv2020

Towards designing globular antimicrobial peptide mimics: role of polar functional groups in biomimetic ternary antimicrobial polymers

Using atomistic molecular dynamics simulations, we study the interaction of ternary methacrylate polymers, composed of charged cationic, hydrophobic and neutral polar groups, with model bacterial membrane. Our simulation data shows that the random ternary polymers can penetrate deep into the membrane interior and partitioning of even a single polymer has a pronounced effect on the membrane structure. Lipid reorganization, on polymer binding, shows a strong affinity of the ternary polymer for anionic POPG lipids and the same is compared with the control case of binary polymers (only cationic and hydrophobic groups). While binary polymers exhibit strong propensity of acquired amphiphilic conformations upon membrane insertion, our results strongly suggest that such amphiphilic conformations are absent in the case of random ternary polymers. The ternary polymers adopt a more folded conformation, staying aligned in the direction of the membrane normal and subsequently penetrating deeper into the membrane interior suggesting a novel membrane partitioning mechanism without amphiphilic conformations. Finally, we also examine the interactions of ternary polymer aggregates with model bacterial membranes, which show that replacing some of the hydrophobic groups by polar groups leads to weakly held ternary aggregates enabling them to undergo rapid partitioning and insertion into membrane interior. Our work thus underscores the role of inclusion of polar groups into the framework of traditional binary biomimetic antimicrobial polymers and suggests different mode of partitioning into bacterial membranes, mimicking antimicrobial mechanism of globular antimicrobial peptides like Defensin.

biophysics↗

bioRxiv2019

Modelling heterogeneities in the cross-linked bacterial sacculus

Examining the design principles of biological materials, in particular the presence of inhomogeneities in their ultrastructure is the key to understanding the often remarkable mechanical properties possessed by them. In this work, motivated by the question of understanding the effect of variability in the material properties of the peptide cross-linkers on the bulk mechanical properties of the cell wall structure of bacteria, we study a spring system in which variability is encoded by assigning values of spring constants and rupture strengths of the constituent springs from appropriate probability distribution. Using analytical methods and computer simulations, we study the response of the spring system to shear loading and observe how heterogeneities inherent in the system can heighten the resistance to failure. We derive the force extension relation of the system and explore the effect that the disorder in values of spring constant and rupture strength has on load carrying capacity of the system and failure displacement. We also study a discrete step shear loading of the system, exhibiting a transition from quasi-brittle to brittle response controlled by the step size, providing possible framework to experimentally quantify the disorder in analogous structures. The model studied here will also be useful in general to understand fiber bundles exhibiting disorder in the elasticity and rupture strengths of constituent fibers.

biophysics↗

bioRxiv2019

The importance of being cross-linked for the bacterial cell wall

The bacterial cell wall is primarily composed of a mesh of stiff glycan strands cross-linked by peptide bridges and is essential for safeguarding the cell. The structure of the cell wall has to be stiff enough to bear the high turgor pressure and sufficiently tough to ensure protection against failure. Here we explore the role of various design features of the cell in enhancing the toughness of the cell wall. We explain how the glycan strand length distribution and the degree of cross-linking can play a vital role in ensuring that the cell wall offers sufficient resistance to propagation of cracks. We suggest a possible mechanism by which peptide bond hydrolysis can also help mitigate this risk of failure. We also study the reinforcing effect of MreB on the cell wall and conclude that the cross-linked structure of the cell wall plays the more important role in safeguarding against mechanical failure due to cracking.

biophysics↗