Light on the interactions between nanoparticles and lipid membranes by interface-sensitive vibrational spectroscopy

Nanoparticles are produced in natural phenomena or synthesized artificially for technological applications. Their frequent contact with humans has been judged potentially harmful for health, and numerous studies are ongoing to understand the mechanisms of the toxicity of nanoparticles. At the macroscopic level, the toxicity can be established in vitro or in vivo by measuring the survival of cells. At the sub-microscopic level, scientists want to unveil the molecular mechanisms of the first interactions of nanoparticles with cells via the cell membrane, before the toxicity cascades within the whole cell. Unveiling a molecular understanding of the nanoparticle-membrane interface is a tricky challenge, because of the chemical complexity of this system and its nanosized dimensions buried within bulk macroscopic environments. In this review, we highlight how, in the last 10 years, second-order nonlinear optical (NLO) spectroscopy, and specifically vibrational sum frequency generation (SFG), has provided a new understanding of the structural, physicochemical, and dynamic properties of these biological interfaces, with molecular sensitivity. We will show how the intrinsic interfacial sensitivity of second-order NLO and the chemical information of vibrational SFG spectroscopy have revealed new knowledge of the molecular mechanisms that drive nanoparticles to interact with cell membranes, from both sides, the nanoparticles and the membrane properties.