Using Optical Tweezers to Characterize Physical Tethers at Membrane Contact Sites: Grab It, Pull It, Set It Free?

Abstract

Compartmentalisation is a defining feature of eukaryotic life. Effective communication between organelles is essential for cell maintenance, growth and response to external stimuli. Static snapshots provided through ultrastructural studies of preserved tissue highlight that certain organelles are in intimate contact at membrane contact sites (MCSs), also referred to as inter-organellar tethering sites. However, live cell imaging indicates that these interactions are not necessarily stable with organelles frequently “colliding,” moving in unison and then separating. This dramatic intracellular “waltz” between organelles with ever changing partners (organelles) indicates that the molecular factors controlling MCSs are highly regulated. Key questions therefore relate to defining which organelles physically interact, deciphering the molecular components that control MCS formation, and ultimately deciphering the specific functional role that the interaction provides to the cell (Figure 1).