Illuminating cell membranes by mixing light

In many ways, life can be defined by membranes. Cell membranes serve as a border between the life inside and the world beyond, and it is through these membranes that cells interact with that world. Small molecules pass through and attach to their surfaces. The membranes also regulate their internal environment and are essential to the structure and shape of the cell.

Page et al. describe how a nonlinear optical technique, second harmonic generation (SHG), can be used to study biological membranes and their interactions with surrounding molecules. They showcase several recent advances enabled by SHG and outline its potential applications for probing membranes.

“SHG studies on bacteria have provided new information on how Gram’s staining works, revealed how an antibiotic drug changes it’s binding depending on ions present in its environment, and shown how small molecules can be modified to change how they move through the membrane,” said author Tessa Calhoun.

SHG involves two photons mixing to form one photon with twice the frequency and requires non-centrosymmetric conditions such as those found in a membrane. Because of the strict symmetry requirements, signals originate predominately from the membrane and unwanted light from the bulk is minimized. The interference behavior of the signal can also be used to detect the presence of small molecules and track their movements from one side of the membrane to the other.

The authors hope their review introduces SHG as a valuable tool to researchers studying biological membranes.

“We also hope our presentation of varying applications of SHG will inspire those researchers already in the field to expand their work in new ways,” said Calhoun.

Source: “Monitoring membranes: The exploration of biological bilayers with second harmonic generation,” by Eleanor F Page, Marea J Blake, Grant A Foley, and Tessa R Calhoun, Chemical Physics Reviews (2022). The article can be accessed at https://doi.org/10.1063/5.0120888 .