Optical Microscopy and the Extracellular Matrix Structure: A Review

Abstract

Biological tissues are not uniquely composed of cells. A substantial part of their volume is extracellular space, which is primarily filled by an intricate network of macromolecules constituting the extracellular matrix (ECM). The ECM serves as the scaffolding for tissues and organs throughout the body, playing an essential role in their structural and functional integrity. Understanding the intimate interaction between the cells and their structural microenvironment is central to our understanding of the factors driving the formation of normal versus remodelled tissue, including the processes involved in chronic fibrotic diseases. The visualization of the ECM is a key factor to track such changes successfully. This review is focused on presenting several optical imaging microscopy modalities used to characterize different ECM components. In this review, we describe and provide examples of applications of a vast gamut of microscopy techniques, such as widefield fluorescence, total internal reflection fluorescence, laser scanning confocal microscopy, multipoint/slit confocal microscopy, two-photon excited fluorescence (TPEF), second and third harmonic generation (SHG, THG), coherent anti-Stokes Raman scattering (CARS), fluorescence lifetime imaging microscopy (FLIM), structured illumination microscopy (SIM), stimulated emission depletion microscopy (STED), ground-state depletion microscopy (GSD), and photoactivated localization microscopy (PALM/fPALM), as well as their main advantages, limitations.

Age-Related Alterations of Hyaluronan and Collagen in Extracellular Matrix of the Muscle Spindles

“…The age-related decrease in HA could affect the mechanical properties of MSs, the background discharge, and the discharge in response to stretch, which may in turn affect age-related changes in MSs’ sensitivity to the stretch and tension of skeletal muscles. As has been demonstrated by other studies, HA has many roles in the different human tissues, ranging from mechanical to chemical [ 19 , 21 , 48 , 51 ].…”

“…Collagens are recognized as the main components of the ECM and form a family of 28 different types of collagens coded for by 44 different genes [ 18 ]. Proteoglycans can be categorized into four main families: small leucine-rich proteoglycans, hylectans, pericellular and basement membrane proteoglycans, and cell-surface proteoglycans [ 19 ]. Hyaluronan (HA) is the major extracellular GAG, which is found in many different tissues and has many roles, ranging from mechanical to chemical [ 19 ].…”

“…Proteoglycans can be categorized into four main families: small leucine-rich proteoglycans, hylectans, pericellular and basement membrane proteoglycans, and cell-surface proteoglycans [ 19 ]. Hyaluronan (HA) is the major extracellular GAG, which is found in many different tissues and has many roles, ranging from mechanical to chemical [ 19 ]. Cell behavior is profoundly affected by the environment in which they live, thus the aging of the ECM is central to understanding age-related changes [ 17 ].…”

“…Cell behavior is profoundly affected by the environment in which they live, thus the aging of the ECM is central to understanding age-related changes [ 17 ]. Nowadays, ECM’s role has been highlighted in different diseases and tissues [ 19 , 20 , 21 , 22 , 23 ].…”

The Functional Role of Extracellular Matrix Proteins in Cancer

“…High-resolution microscopy techniques, for instance, second harmonic generation (SHG) or coherent anti-Stokes Raman scattering (CARS), are successfully used to quantify tissue structural changes during cancer progression [ 375 , 376 ]. It was also reported about the combined use of SHG microscopy and mass spectrometry [ 377 ].…”