BPS2026 – Investigating malaria parasite membrane contact site domain coarsening and boundary fluctuations

The malaria parasite, Plasmodium falciparum , causes the deadliest form of malaria exponentially replicating in host-red blood cells. The parasite interfaces with the host-cell through a structure consisting of the parasite’s own plasma membrane (the parasite plasma membrane, PPM) and an enveloping membrane (the parasitophorous vacuole membrane, PVM). These two membranes form a bimodal spacing with domains (regions) of close membrane apposition (∼3–4 nm aqueous space in between membranes) and domains of far membrane apposition (20–40 nm), that correlate with lipid transport and protein export/nutrient trafficking, respectively. Quantification of the domain sizes during the second day of development shows domain growth from sub-μm to several μm reminiscent of a phase transition and cooling of a two-phase system. To describe this behavior, we propose the definition of an effective temperature (T eff ) for the host-parasite interface. We hypothesize that T eff could be used to quantify transport activity across the host-parasite interface and are testing the idea by quantifying T eff with treatments affecting various aspects of the known trafficking machinery. Our goal is to develop a universal measure for activity at the malaria parasite—host-red blood cell interface. Moreover, we hope to gain insight into the role of membrane contact site forming proteins in creating the parasite’s close membrane appositions.