Research Area

Study of Line Tension and its Impact on Protein Organization in Model Domain-Forming Membranes

Membrane domains, commonly referred to as lipid rafts, play a crucial role in numerous cellular processes; however, the factors governing their stability and associated protein organization remain debated. Here, we employ coarse-grained molecular dynamics simulations to systematically investigate the molecular determinants of interfacial line tension and its role in membrane organization. We first demonstrate that capillary wave theory provides reliable estimates of line tension, provided that boundary fluctuations are adequately sampled. Our results reveal that domain stability is not primarily controlled by hydrophobic thickness mismatch; instead, it is governed by differences in molecular packing, quantified by the order parameter difference (ΔP2) between coexisting phases. Sterols, key components of biological membranes, modulate interfacial properties in a non-monotonic manner, with maximal domain stability observed at intermediate concentrations of around 10–15%. Furthermore, we find that transmembrane protein localization does not universally minimize line tension, but is instead dictated by hydrophobic thickness mismatch and specific lipid–protein interactions. These findings provide new mechanistic insights into the molecular origins of membrane domain stability and highlights the factors that regulate the spatial organization of transmembrane proteins at domain interfaces.

Published in PCCP.

Controlling Spatial Organization of HIV Coreceptor CCR5

CC chemokine receptor type 5 (CCR5) functions as a key coreceptor facilitating HIV entry into host cells. Recent experimental findings suggest that CCR5 preferentially localizes at lipid domain boundaries within the host cell membrane, where its positioning enhances viral fusion efficiency by allowing the HIV fusion peptide gp41 to exploit the mechanically weaker interface regions. In this study, we employ coarse-grained molecular dynamics simulations to investigate the spatial organization of CCR5 within domain forming model membranes. Our results reveal a molecular mechanism by which CCR5 preferentially migrates and stabilizes at domain boundaries. Additionally, we show that lysophosphatidylcholine (lysoPC) lipids, acting as linactants, accumulate at domain interfaces, reduce line tension, and ultimately disrupt membrane domain organization. This disruption leads to a delocalization of CCR5, potentially impairing the ability of gp41 to target membrane boundaries for fusion. Together, our findings suggest that linactants may be employed to disrupt the spatial organization of CCR5, potentially hindering HIV’s ability to initiate membrane fusion and entry.

Published in JCIM.

How Are Plastoglobules Formed in Green Algae?

Plastoglobules are droplet-like organelles with a hydrophobic core of neutral lipids surrounded by a lipid monolayer, usually found in the chloroplasts of most plants and green algae. They not only serve as lipid storage units in the thylakoid membranes but are also involved in many cellular processes, including photoprotection, metabolite synthesis, protein recruitment, and chloroplast differentiation. Unlike lipid droplets, which nucleate, grow, and subsequently detach from the endoplasmic reticulum (ER) membrane, plastoglobules remain permanently coupled to the stromal side of the thylakoid membrane. In this study, we employ molecular dynamics simulations to investigate the growth mechanism of plastoglobules in a model thylakoid membrane of Dunaliella algae. Our findings suggest that significant membrane remodeling, likely driven by the thylakoid membrane proteins, is essential for the directional growth and stability of the plastoglobules.

Published in J. Phys. Chem. Lett.

Origin of the Nonlinear Structural and Mechanical Properties in Oppositely Curved Lipid Mixtures

Structural and mechanical properties of membranes such as thickness, tail order, bending modulus and curvature energetics play crucial role in controlling various cellular functions that depend on the local lipid organization and membrane reshaping. While behavior of these biophysical properties are well understood in single component membranes, very little is known about how do they change in the mixed lipid membranes.

Often various properties of the mixed lipid bilayers are assumed to change linearly with the mole fractions of the constituent lipids which, however, is true for “ideal” mixing only. In this study, using molecular dynamics simulations, we show that structural and mechanical properties of binary lipid mixture change nonlinearly with the lipid mole fractions, and the strength of the nonlinearity depends on two factors - spontaneous curvature difference and locally inhomogeneous interactions between the lipid components.

Published in J. Chem. Phys.

Functional membrane microdomains (FMMs) formation in bacterial membranes

Recent experimental studies revealed that functional membrane microdomains (FMMs) are formed in prokaryotic cells which are structurally and functionally similar to the lipid rafts formed in eukaryotic cells. We employ coarse-grained molecular dynamics simulations to investigate the mechanism of domain formation and its physiochemical properties in a model methicillin-resistant staphylococcus aureus (MRSA) cell membrane.

We find that domains are formed through lateral segregation of staphyloxanthin (STX), a carotenoid which shields the bacteria from the host's immune because of its antioxidant nature. Simulation results suggest that membrane integrity increases with the size of the domain and various membrane domain proteins such as flotillin-like protein floA and penicillin binding protein (PBP2a) preferentially bind with the STX and accumulate in the membrane domain which is consistent with the recent experimental results.

Published in PCCP