Agnes B. Kane, M.D., Ph.D.
An NIEHS grantee and colleagues identified a nanochemical mechanism through which long and stiff carbon nanotubes damage lysosomes — membrane-enclosed organelles that break down damaged or unneeded biomolecules and debris inside the cell. The new findings could help scientists design safer nanomaterials.
Recent experimental studies have shown links between carbon nanotube toxicity and tube length and stiffness. However, scientists do not fully understand the reason for this or what happens to carbon nanotubes once they are inside cells. In the new work, the researchers combined analytical modeling, molecular dynamics simulations, and intracellular imaging of liver and lung cells, to form a picture of how one-dimensional carbon nanotubes behave inside lysosomes.
The researchers found that lysosomal membranes compressed long, stiff nanotubes, causing the nanotube tip to persistently contact the inner membrane. This contact led to the removal of lipids making up the membrane, increased permeability of the lysosome, released lysosomal protease into the cytoplasm, and eventually cell death. The researchers also created a classification diagram that shows the minimum and maximum nanotube dimensions required for this harmful process to occur for a wide variety of materials, including metals, oxides, and polymers.
Citation: Zhu W, von dem Bussche A, Yi X, Qiu Y, Wang Z, Weston P, Hurt RH, Kane AB, Gao H. Nanomechanical mechanism for lipid bilayer damage induced by carbon nanotubes confined in intracellular vesicles. Proc Natl Acad Sci U S A 113(44):12374-12379.