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- Title
A noninvasive fluorescence imaging-based platform measures 3D anisotropic extracellular diffusion.
- Authors
Chen, Peng; Chen, Xun; Hepfer, R. Glenn; Damon, Brooke J.; Shi, Changcheng; Yao, Jenny J.; Coombs, Matthew C.; Kern, Michael J.; Ye, Tong; Yao, Hai
- Abstract
Diffusion is a major molecular transport mechanism in biological systems. Quantifying direction-dependent (i.e., anisotropic) diffusion is vitally important to depicting how the three-dimensional (3D) tissue structure and composition affect the biochemical environment, and thus define tissue functions. However, a tool for noninvasively measuring the 3D anisotropic extracellular diffusion of biorelevant molecules is not yet available. Here, we present light-sheet imaging-based Fourier transform fluorescence recovery after photobleaching (LiFT-FRAP), which noninvasively determines 3D diffusion tensors of various biomolecules with diffusivities up to 51 µm2 s−1, reaching the physiological diffusivity range in most biological systems. Using cornea as an example, LiFT-FRAP reveals fundamental limitations of current invasive two-dimensional diffusion measurements, which have drawn controversial conclusions on extracellular diffusion in healthy and clinically treated tissues. Moreover, LiFT-FRAP demonstrates that tissue structural or compositional changes caused by diseases or scaffold fabrication yield direction-dependent diffusion changes. These results demonstrate LiFT-FRAP as a powerful platform technology for studying disease mechanisms, advancing clinical outcomes, and improving tissue engineering. It is challenging to quantify anisotropic diffusion in biological systems. Here the authors report light-sheet imaging-based Fourier transform fluorescence recovery after photobleaching (LiFT-FRAP) to noninvasively determine 3D diffusion tensors of various biomolecules at physiological diffusivity.
- Subjects
BIOLOGICAL systems; DIFFUSION measurements; BIOLOGICAL transport; TREATMENT effectiveness; FOURIER transforms; TISSUE scaffolds; MOLECULAR communication (Telecommunication)
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-22221-0