Controlling Transport of Nanomaterial Across Cell Membrane by Tuning Membrane Tension

Growing awareness of toxicity and bioeffects of nanomaterials interacting with cells brings into focus the mechanisms by which nanomaterials can cross lipid membranes. Besides well-deliberated energy-dependent endocytosis for large objects and passive diffusion via membranes by solute molecules, there can be other transport mechanisms based on physical principles.

Based on this theory, a team of theoretical physics at Universitat Rovira i Virgili in Tarragona, led by Dr. Vladimir Baulin, planned a research project to study the interaction between nanotube and lipid membranes. In computer simulations, the scientists analyzed what they term a “model bilayer”, made up of only by one type of lipids. Based on their calculations, the team of Dr. Baulin noted that ultra-short nanotube (10 nm length) can insert perpendicularly to the lipid bilayer core.

They learned that these nanotubes remain trapped in the cell membrane, as broadly accepted by the scientific community. But a revelation is revealed when they stretched their model cell membrane, and then inserted nanotubes that were stuck in the bilayer, suddenly began to escape from the bilayer on both sides. This means that it is possible to regulate the movement of nanomaterial across a cell membrane by tweaking the membrane tension.

This is where Dr. Baulin reached out to Dr. Jean-Baptiste Fleury at the Saarland University (Germany) to confirm this mechanism and to examine experimentally this tension-mediated transport occurrence. Dr. Fleury and his team prepared a microfluidic experiment with a well-controlled phospholipid bilayer, an experimental model for cell membranes and integrated ultra-small carbon nanotubes (10 nm in length) in solution. The nanotubes had an adsorbed lipid monolayer that ensures their steady dispersion and thwarts their clustering.

Using a combination of optical fluorescent microscopy and electrophysiological measurements, the team of Dr. Fleury could trail individual nanotube crossing a bilayer and unravel their pathway on a molecular level. Plus, as predicted by the simulations, they noted that nanotubes inserted into the bilayer by dissolving their lipid coating into the artificial membrane. When a tension of 4 mN/m was applied to the bilayer, nanotubes suddenly escaped the bilayer within a few milliseconds, while at lower tensions nanotubes stay trapped inside the membrane.

This detection of translocation of miniature nanotubes through barriers safeguarding cells, i.e. lipid bilayer, may raise doubts regarding the safety of nanomaterials for public health and propose new mechanical mechanisms to regulate drug delivery.