The Organization of Membranes Below 100 nm: Experimental Breakthroughs Occasion a Modeling Manifesto

Abstract

New experimental techniques reveal the plasma membrane to be heterogeneous and \"scale-rich,\" from nanometers to microns, and from microseconds to seconds. This is critical information, as heterogeneous, scale-dependent transport governs the molecular encounters that underlie cellular signaling. The data are rich, and reaffirm the importance of the cortical cytoskeleton, protein aggregates, and lipidomic complexity to the statistics of molecular encounters. Moreover, the data demand simulation approaches with a particular set of features, hence the \"manifesto\". Together with the experimental data, simulations which satisfy these requirements hold the promise of a deeper understanding of membrane spatiotemporal organization. Several experimental breakthroughs are reviewed, the constraints that they place on simulations are discussed, and the status of simulation approaches which aim to meet them are detailed.