1. The self-assembly of lipoteichoic acid (LTA) in aqueous solutions:
The LTA aggregates play a major role in the process of bioadhesion and colonisation, which are responsible for initiation of bacterial infections. Considering the amphiphilic structure of LTA, its aggregation behavior in water may reveal interesting structural features. The self-assembly of LTA in water and their adsorption behavior at the air-water and air-solid interfaces are interesting to understand their role in the post-infection sequalae. The microscopic images indicated formation of spherical aggregates that do not adsorb considerably on charged silica surface, while on rinsing with Ca2+ ions, the adsorption increases significantly indicating role of Ca2+ ions in LTA binding on charged surfaces. We also examined these structures by DLS and SANS methods, which indicated decrease in size of LTA aggregates on Ca2+ addition.
2. Effect of LTA on mixed vesicles containing phospholipids (soft nanohybrids):
The lipoteichoic acid (LTA) is tethered directly to the hydrocarbon chain of phospholipids in the actual membrane, and accordingly influences the structural stability and integrity of the phospholipid membrane. We investigated the effect of LTA on mixed vesicles (representing the bilayer phospholipid membrane) by scattering and microscopy methods. The mixed vesicles containing LTA and phospholipids, namely phosphatidyl glycerol (PG), phosphatidyl ethanolamine (PE) and cardiolipin (C16:0) were prepared by film drying method. LTA composition in the membrane is regulated by bacteria under different physiological conditions. How such LTA compositional variations modulate the membrane structural stability and integrity is poorly understood. Here, we have investigated structural changes in mixed liposomes mimicking the lipid composition of Gram-positive bacteria membranes, in which the concentration of Bacillus Subtilis LTA was varied between 0–15 mol%. Small-angle neutron scattering (SANS) and dynamic light scattering (DLS) measurements indicated formation of mixed unilamellar vesicles, presumably stabilized by the negatively charged LTA polyphosphates. The vesicle size increased with the LTA molar concentration up to ∼6.5 mol%, accompanied by a broadened size distribution, and further increasing the LTA concentration led to a decrease in the vesicle size. This work was published in Colloids and Surfaces B: Biointerfaces (Bhavesh Bharatiya, Gang Wang, Sarah E. Rogers, Jan Skov Pedersen, Stephen Mann, Wuge H. Briscoe*, Colloids and Surfaces B: Biointerfaces, 2021, 199, 111551. Gold Open Access.
The fellow also worked in collaborative projects with colleagues at the Bristol University and a research center in India.
3. The design and formulation of Exemestane formulation for breast cancer treatment :
We designed liquid crystalline (LC) formulation of Exemestane using Pluronic block copolymer P85/P84 and propylene glycol as cosolvents in a suitable oil media. This formulation containing thermoresponsive lamellar liquid crystal gels of EXE represented a viable option for hyperthermia induced enhanced drug release. This work was accomplished in collaboration with Dr V Shah at Shah-Schulman Research Center, India.
4. The effect of cations on self-assembly behaviour of Gram-negative bacterial lipopolysaccharide (LPS) :
Lipopolysaccharide (LPS) is a key structural component of the outer membrane of gram-negative bacteria. LPS is a macromolecule with six hydrophobic tails and a very long hydrophilic headgroup which shows a very complex aggregation behaviour forming a wide variety of structures in solution. Cations are known to be crucial for the integrity of the bacterial out membrane and can complex with LPS which affects bacterial membrane integrity and LPS virulence. To develop effective and alternative antibacterial agents, it is crucial to understand the structure of, and fundamental interactions at, the bacterial cell wall. Here, the effects of monovalent (Na+), divalent (Ca2+), and trivalent cations (La3+), as well as LPS carbohydrate head group length on the structure, size and electrostatic properties of LPS aggregates at near physiological conditions are studied. This work was done in collaboration with Dr Gang Wang, Marie Curie fellow, University of Bristol. A manuscript based on this work is under preparation.
