# Monitoring Molecular Interactions with Cell Membranes Using Time-Dependent Second Harmonic Generation Microscopy

## TL;DR

This study uses advanced microscopy to track how drug-like molecules interact with cell membranes in living and dead lung cancer cells.

## Contribution

The novel use of time-resolved SHG microscopy reveals real-time molecular adsorption and transport dynamics across cell membranes.

## Key findings

- MGITC shows stronger adsorption and faster transport than MG due to dipole–dipole interactions.
- MGITC transport is faster in living versus fixed cells, indicating changes in membrane integrity.
- Electrostatic interactions and chemical groups influence molecular translocation dynamics.

## Abstract

Time-resolved second
harmonic generation (SHG) microscopy is used
to investigate the physicochemical interactions between positively
charged, hydrophobic, drug-like molecules and the plasma membrane
of human cells (nonsmall cell lung cancer, H596). In the present study,
molecular adsorption and transport of the cationic molecules, malachite
green (MG) and malachite green isothiocyanate (MGITC), are studied
in real time in living H596 cells and in dead, fixed H596 cells. MGITC
is shown to have stronger adsorption and more rapid transport kinetics
as compared to MG due to increased dipole–dipole interactions.
Additionally, MGITC is found to have faster adsorption and transport
kinetics in living H596 cells in comparison to fixed H596 cells, as
well as higher dispersity in transport rate, pointing to changes in
the nature of the plasma membrane or its integrity. Overall, the findings
highlight the importance of electrostatic interactions, chemical functional
groups, and cell integrity in molecular translocation dynamics across
cell membranes.