Live imaging of the brain extracellular matrix (ECM) provides vital insights into changes that occur in neurological disorders. Current techniques such as second or third‐harmonic generation offer limited contrast for live imaging of the brain ECM. Here, a new method, pan‐ECM via chemical labeling of extracellular proteins, is introduced for live brain ECM imaging. pan‐ECM labels all major ECM components in live tissue including the interstitial matrix, basement membrane, and perineuronal nets. pan‐ECM enables in vivo observation of the ECM heterogeneity between the glioma core and margin, as well as the assessment of ECM deterioration under stroke condition, without ECM shrinkage from tissue fixation. These findings indicate that the pan‐ECM approach is a novel way to image the entire brain ECM in live brain tissue with optical resolution. pan‐ECM has the potential to advance the understanding of ECM in brain function and neurological diseases.
Extracellular vesicles (EVs) influence a host of normal and pathophysiological processes in vivo. Compared to soluble mediators, EVs can traffic a wide range of proteins on their surface including extracellular matrix (ECM) binding proteins, and their large size (∼30‐150 nm) limits diffusion. We isolated EVs from the MCF10 series—a model human cell line of breast cancer progression—and demonstrated increasing presence of laminin‐binding integrins α3β1 and α6β1 on the EVs as the malignant potential of the MCF10 cells increased. Transport of the EVs within a microfluidic device under controlled physiological interstitial flow (0.15‐0.75 μm/s) demonstrated that convection was the dominant mechanism of transport. Binding of the EVs to the ECM enhanced the spatial concentration and gradient, which was mitigated by blocking integrins α3β1 and α6β1. Our studies demonstrate that convection and ECM binding are the dominant mechanisms controlling EV interstitial transport and should be leveraged in nanotherapeutic design.
more » « less- NSF-PAR ID:
- 10408737
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Extracellular Vesicles
- Volume:
- 12
- Issue:
- 4
- ISSN:
- 2001-3078
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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