Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Thursday Speaker Abstracts

BIOPHYSICS OF EPHA2 RECEPTOR SIGNALING IN THE MEMBRANE Kalina Hristova Johns Hopkins University, Baltimore, MD, USA EphA2 is expressed in the brain and plays a critical role in axon guidance. Its mechanism of signal transduction is not fully understood despite very active research in the field. We have observed that microscopic GM1-enriched domains can form, in the plasma membrane of live mammalian cells expressing the EphA2 receptor tyrosine kinase, in response to its ligand ephrinA1-Fc. The GM1-enriched microdomains form concomitantly with EphA2-enriched microdomains. To gain insight into how plasma membrane heterogeneity controls signaling, we quantified the degree of EphA2 segregation and we studied the initial EphA2 signaling steps in both EphA2-enriched and EphA2-depleted domains using Forster Resonance Energy transfer and Number and Brightness. By measuring dissociation constants, we demonstrate that the propensity of EphA2 to oligomerize is similar in EphA2-enriched and -depleted domains. However, EphA2 interacts preferentially with its downstream effector SRC in EphA2-depleted domains. Given the critical role of EphA2 organization for signaling, we are using MINFLUX imaging as we seek detailed views of the EphA2-enriched and -depleted domains and mechanistic insights into oligomerization and domain formation.

42