Molecular Rotors: Fluorescent Sensors for Microviscosity and Conformation of Biomolecules

Abstract

The viscosity and crowding of biological environment are considered vital for the correct cellular function, and alterations in these parameters are known to underly a number of pathologies including diabetes, malaria, cancer and neurodegenerative diseases, to name a few. Over the last decades, fluorescent molecular probes termed molecular rotors proved extremely useful for exploring viscosity, crowding, and underlying molecular interactions in biologically relevant settings. In this review, we will discuss the basic principles underpinning the functionality of these probes and will review advances in their use as sensors for lipid order, protein crowding and conformation, temperature and non‐canonical nucleic acid structures in live cells and other relevant biological settings.

High-throughput analysis of membrane fluidity unveils a hidden dimension in immune cell states

“…Our flow pipeline is highly versatile in multiplex capability and scope (e.g., several biophysical properties of intracellular membranes can also be investigated by means of smart probes which target subcellular organelles or report on different properties like membrane viscosity, tension etc.) 54 and it can be easily integrated with any commercial flow cytometer. Remodelling of cell biophysics continues to gain attention as an active player in defining health and diseases, and the present work represents the first effort towards establishing PM fluidity as a new parameter orthogonal to classical multi-omics analysis in molecular biology and bringing cell biophysics into biomedical practises.…”

Exploration of Novel Meso-C═N-BODIPY-Based AIE Fluorescent Rotors with Large Stokes Shifts for Organelle-Viscosity Imaging

“…Fluorescent rotors for viscosity have attracted increasing attention in recent years and have served as important tools to monitor microenvironmental viscosity changes in biological systems. − An organic small-molecular rotor mainly consists of a fluorophore and a rotation moiety, and its emission is efficiently quenched by the rotation, which can be enhanced in viscous or steric environments through inhibited rotation. − Among intracellular viscosities, the balance of subcellular lysosomal and mitochondrial viscosities was crucial to maintain the normal subcellular physiological activities in their closed systems. Abnormal fluctuations of lysosomal viscosity could cause many diseases, for example, lysosomal storage diseases, inflammation and neurodegenerative diseases, and cardiovascular diseases. − Meanwhile, the variations of mitochondrial viscosity were closely related to atherosclerosis, cellular malignancy, and dysfunctions. − Recently, various fluorescent probes for sensing subcellular viscosity have been constructed by decorating a targeting group to the rotatable fluorophore, − in which morpholines and ammonium/phosphonium salts , were commonly used as targeting groups for lysosomes and mitochondria, respectively. Therefore, the research on small-molecule fluorescent probes for sensing the subcellular viscosity is still an important and hot topic to gain a full understanding of the relationships between subcellular viscosity and related diseases.…”