When do cell membranes rupture?

Electrical recordings of delivery of drugs inside cells is a cornerstone of modern biotechnology. However, how materials enter or penetrate the cell wall is still something of a mystery. We show a new technique that demonstrates the ability of different materials and surfaces to cause membrane rupture.

HFSP Program Grant holders Nick Melosh and Andreas Schaeffer and colleagues
authored on Tue, 01 September 2015

Electrical recordings of cell activity or delivery of drugs or genetic material inside cells is critical for cell manipulation and testing. However, gaining entry into the cell is still relatively challenging, and no universal method exists yet.  This is partly due to the remarkable properties of cell membrane itself, which prevents foreign material and objects from entering the cell, while specialized proteins act as gatekeepers for particular chemicals.

Figure: Penetration of cell walls is a critical component for drug delivery and cell manipulation. Here we use ultra-sensitive atomic force microscopy to measure the force and position of different species as they penetrate through the lipid bilayer. The black trace shows the pathway taken by the materials while pushing through two lipid bilayers, shown schematically.

We investigated how materials that are coated with various chemical species interact with the cell membrane, and examined whether any could facilitate membrane rupture, providing a simple means of breaching the cell wall. We used an ultra-sensitive force measurement probe, known as an atomic force microscope, to press different coatings into cells and measured when the cells ruptured. We discovered that the set of commonly-believed membrane-disrupting molecules did not in fact cause membrane disruption, or dramatically alter the mechanical penetration mechanism. When we then tested plain synthetic membranes without external proteins and complex membrane structure in living cells, we observed very similar results. This reveals that the mechanics of the lipid bilayer that composes the cell wall is in fact the true barrier for penetration, and that the additional proteins and sugars in the cell do not play a crucial role in determining membrane strength, contrary to previous assumptions. This insight allows new cell-permeant materials based on the lipid bilayer itself to be designed, and provides a clearer path towards seamless cellular access.


Penetration of Cell Membranes and Synthetic Lipid Bilayers by Nanoprobes. Matthew R. Angle, Andrew Wang, Aman Thomas, Andreas T. Schaefer, and Nicholas A. Melosh. Biophysical Journal, pp. 2091-2100, 2014. doi:10.1016/j.bpj.2014.09.023

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