Protein secretion is an essential process in cell physiology, responsible for the release of proteins such as collagens, insulin, neurotransmitters, and many others. To achieve this, proteins follow the so-called secretory pathway, which begins at the endoplasmic reticulum (ER). Thus, the first and fundamental step is the export of proteins from the ER. However, the mechanisms by which diverse cargoes (from small soluble proteins to large and complex molecules) are selectively sorted and packaged for export remain incompletely understood. In this talk, I will present our current experimental and theoretical approaches to uncover the biophysical principles governing ER export.

First, using a single-molecule microscopy technique (single-particle tracking, sptPALM), we directly probe the dynamic behavior of secretory proteins at ER exit sites in living cells, with spatial and temporal resolutions of ~10 nm and 10 ms. These measurements reveal how molecular mobility, confinement, and interactions contribute to cargo selection and concentration prior to export.

Second, I will introduce a physical modeling framework that captures the formation and function of export carriers, with a particular focus on large cargoes that challenge conventional vesicular transport mechanisms. The model highlights how physical constraints such as membrane deformation, crowding, and protein self-organization shape export efficiency and carrier architecture.

Together, these complementary approaches are beginning to provide a quantitative view of ER export as an emergent process arising from the interplay between molecular interactions and membrane mechanics.