Using Nanoparticles to Control Cellular Membrane Potential

Abstract

All cells generate an electrical potential (Vm) across their plasma membrane driven by a concentration gradient of charged ions. A typical resting membrane potential ranges from −40 to −70 mV, with a net negative charge on the cytosolic side of the membrane. Disruption of this electrochemical equilibrium causes Vm to become more positive or more negative relative to its resting state, referred to as “depolarization” or “hyperpolarization,” respectively. Changes in membrane potential have proven to be pivotal not only in normal cell cycle progression, but also in malignant transformation. Using polystyrene nanoparticles as a model system, we use a combination of fluorescence microscopy and flow cytometry to measure changes in membrane potential in response to nanoparticle binding to the plasma membrane. We find that cationic nanoparticles depolarize both CHO-K1 and HeLa cells. The cellular binding of anionic nanoparticles does not lead to a discernible trend in altered membrane potential. Maintenance of the resting membrane potential depends on the presence of two-pore-domain potassium “leak” channels, which allow for outward diffusion of potassium ions along their concentration gradient. Using an assay that tests the diffusion of ions through these potassium channels, we observe reduced permeability of the channels when cells are treated with nanoparticles. Based on a dynamical system model of the cell, we conclude that this loss of permeability likely results from physical blockage of the channel itself by the particle. Prevention of potassium ion efflux due to blocked channels causes accumulation of positive charge inside the cell, resulting in a depolarized membrane. By understanding the ways in which nanoparticles can be utilized to selectively generate cellular responses, we can begin to consider them as active species that may alter the very systems they are currently designed to probe.