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.

Fast Recombination of Free Radicals in Solution and Microviscosity

“…The local viscosity or η micro supposedly plays an important role in biology across several length scales [23]. There is growing evidence that the fluidity of the cell's lipid plasma membrane is regulated to enable optimal cellular function, and η micro within the cell's nucleus may influence the formation of non-canonical DNA assemblies [23].…”

“…The local viscosity or η micro supposedly plays an important role in biology across several length scales [23]. There is growing evidence that the fluidity of the cell's lipid plasma membrane is regulated to enable optimal cellular function, and η micro within the cell's nucleus may influence the formation of non-canonical DNA assemblies [23]. However, unlike in the cases of bulk industrial applications (see above), including additive manufacturing, biological viscosity is challenging to measure and requires the development of methodologies that can probe viscoelastic properties of microscopic volumes of individual biological cells and organelles [23].…”

“…There is growing evidence that the fluidity of the cell's lipid plasma membrane is regulated to enable optimal cellular function, and η micro within the cell's nucleus may influence the formation of non-canonical DNA assemblies [23]. However, unlike in the cases of bulk industrial applications (see above), including additive manufacturing, biological viscosity is challenging to measure and requires the development of methodologies that can probe viscoelastic properties of microscopic volumes of individual biological cells and organelles [23]. While a myriad of different dyes have been developed to study the microenvironment of lipid membranes, Molecular fluorescent rotors give valuable η micro of their surroundings in a biological object [23].…”

“…However, unlike in the cases of bulk industrial applications (see above), including additive manufacturing, biological viscosity is challenging to measure and requires the development of methodologies that can probe viscoelastic properties of microscopic volumes of individual biological cells and organelles [23]. While a myriad of different dyes have been developed to study the microenvironment of lipid membranes, Molecular fluorescent rotors give valuable η micro of their surroundings in a biological object [23]. At the same time, many developed dyes-probes of η micro often respond to multiple biophysical features and/or are not fully calibrated against the various membrane parameters [23].…”

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.…”