Beyond Langmuir: surface-bound macromolecule condensates.

Macromolecule condensates, phase separation, and membraneless compartments have become an important area of cell biology research where new biophysical concepts are emerging. This article discusses the possibility that condensates assemble on multivalent surfaces such as DNA, microtubules, or lipid bilayers by multilayer adsorption. Langmuir isotherm theory conceptualized saturable surface binding and deeply influenced physical biochemistry. Brunauer-Emmett-Teller (BET) theory extended Langmuir's ideas to multilayer adsorption. A BET-inspired biochemical model predicts that surface-binding proteins with a tendency to self-associate will form multilayered condensates on binding surfaces. These "bound condensates" are expected to assemble well below the saturation concentration for liquid-liquid phase separation, so they can compete subunits away from phase-separated droplets and are thermodynamically pinned to the binding surface. Tau binding to microtubules is an interesting test case. The nonsaturable binding isotherm is reminiscent of BET predictions, but assembly of Tau-rich domains at low concentrations requires a different model. Surface-bound condensates may find multiple biological uses, particularly in situations where it is important that condensate assembly is spatially constrained, such as gene regulation.