The cell plasma membrane serves not only as a protective barrier but as the first responder to a changing environment. One environmental challenge these cells face is osmotic stress — where an imbalance of, for instance, ions or sugars, across the plasma membrane exerts osmotic pressure on the membrane. In order to deal with osmotic stress, mammalian cells have evolved complex protein machineries. But how do simpler cells respond to an osmotic onslaught? We answer this question by studying cell-sized lipid vesicles in osmotic stress. Surprisingly, they display a pulsatile behavior, swelling, bursting, and resealing their membrane cycle after cycle!

The cover image for the April 25 issue of the Biophysical Journal is an artistic rendering of the pulsatile dynamics of cell-sized vesicles in osmotic stress. The red fluorescent vesicles represent experimental observations of giant unilamellar vesicles at three stages of the osmotic swell-burst cycle: relaxed (left), swollen (middle), and ruptured with a burst of fluorescent green sucrose (right). On the piece of paper, the vesicles are projected onto corresponding schematics depicting the different stages of the cycle. The leading processes driving the pulsatile behavior, osmotic pressure, surface tension, and leak-out velocity, are defined in mathematical terms. On the top-right of the paper, is one of the key equations we proposed, representing the dynamics of a pore in the membrane taking into account stochastic pore nucleation induced by thermal fluctuations.

This cover was inspired by the combined experimental and theoretical approaches we embraced in this study. It shows how, from experimental observations (the red vesicles), a conceptual model can be built and formalized into mathematical terms (the schematics) to understand the underlying mechanisms of pulsatile vesicles. By mirroring “realistic” vesicles with “hand-drawn” schematics, the cover illustrates how the complexity of a real world process can be reduced to its essential features through modeling. This fundamental scientific approach allows us to build a testable hypothesis to unravel the biophysical principles behind experimental observations.

Through our study and this cover, we highlight how combining experimental and theoretical approaches can be a powerful way to tackle complex challenges, especially for fundamental problems at the frontier between biology, chemistry, and physics.

—Morgan Chabanon, James CS Ho, Bo Liedberg, Atul Parikh, Padmini Rangamani