Biology subjects

Vogt, E. J. D.

Publications and source records attributed to Vogt, E. J. D..

3 recordsLinked to original sources

bioRxiv2025

Lipid packing and local geometry influence septin curvature sensing

Septins assemble into scaffolds that direct cell growth and morphology that are often localized to the plasma membrane. While septins preferentially bind convex membranes via amphipathic helices, their assembly on varied geometries in cells suggests additional localization cues. We tested the hypothesis that lipid composition directs septin assembly through lipid packing properties. Lipid mixtures varying in lipid packing were designed by molecular dynamics simulations and incorporated onto supported lipid bilayers to measure septin adsorption in vitro. Septins strongly favor loosely-packed, disordered lipid bilayers but additional geometry cues act in conjunction with this membrane property. Introducing tighter lipid packing in cells disrupted septin structures in a curvature dependent manner, specifically limiting septin assembly and retention along flat regions of the plasma membrane. This work demonstrates that packing defects and geometry jointly regulate septin localization and highlights how multiple membrane properties are integrated to control organization of the septin cytoskeleton. SummaryLocalization of the septin cytoskeleton is controlled by regulatory factors, membrane curvature, and charge. In this study, changes to lipid composition that modulate lipid packing defects are found to impact septin assemblies in vitro and in cells.

biochemistry↗

bioRxiv2024

Charge distribution and helical content tune the binding of septins amphipathic helix domain to lipid membranes

Septins are a class of cytoskeletal proteins that preferentially bind to domains of micron-scale curvature on the cell membrane. Studies have shown that amphipathic helix (AH) domains in septin oligomers are essential for septin curvature sensing. Yet, the underlying mechanochemical interactions that modulate this curvature sensing remain ambiguous. Here we use all-atom molecular dynamics alongside a metadynamics enhanced sampling approach to bridge the gap between time and length scales required to optimize and validate experimental design of amphipathic helices. Simulations revealed that the local charge on the termini of an 18-amino-acid AH peptide impacts its helical content and positioning within lipid membranes. These computational observations are confirmed with experiments measuring the binding of synthetic AH constructs with variable helical content and charged termini to lipid vesicles. Taken together, these results identify the helical content of amphipathic helices as a regulator of septin binding affinity to lipid membranes. Additionally, we examined an extended AH sequence including 8 amino acids upstream and downstream of the minimal 18-amino-acid-long AH domain to more closely mimic the native protein in simulations and experiments. Simulations and experiments show that the extended peptide sequence adopts a strong alpha-helical conformation when free in solution, giving rise to a higher affinity to lipid membranes than that of the shorter AH sequence. Together, these results provide insight into how the native septin proteins interact with membranes, and establish general design principles that can guide the interaction of future synthetic materials with lipid membranes in a programmable manner. STATEMENT OF SIGNIFICANCEUnderstanding how cells sense and react to their shape is necessary for numerous biological processes. Here we explore the interactions between amphipathic helices, a curvature sensing protein motif, and lipid membranes. Using molecular dynamics simulations, enhanced simulation sampling techniques, and experiments, we find that increasing the helical content of the amphipathic helix or adding charged capping sequences yields higher membrane binding affinity. Understanding these parameters for membrane-binding could enable us to interface and regulate native protein functions, as well as guide the design of synthetic curvature-sensing materials that can interact with and deform lipid membranes.

biophysics↗

bioRxiv2019

Unconventional cell division cycles from marine-derived yeasts

Fungi have been found in every marine habitat that has been explored, however, the diversity and functions of fungi in the ocean are poorly understood. In this study, fungi were cultured from the marine environment in the vicinity of Woods Hole, MA, USA including from plankton, sponge and coral. Our sampling resulted in 36 unique species across 20 genera. We observed many isolates by time-lapse differential interference contrast (DIC) microscopy and analyzed modes of growth and division. Several black yeasts displayed highly unconventional cell division cycles compared to those of traditional model yeast systems. Black yeasts have been found in habitats inhospitable to other life and are known for halotolerance, virulence, and stress-resistance. We find that this group of yeasts also shows remarkable plasticity in terms of cell size control, modes of cell division, and cell polarity. Unexpected behaviors include division through a combination of fission and budding, production of multiple simultaneous buds, and cell division by sequential orthogonal septations. These marine-derived yeasts reveal alternative mechanisms for cell division cycles that seem likely to expand the repertoire of rules established from classic model system yeasts.

cell biology↗