Chemoselective Characterization of New Extracellular Matrix Deposition in Bioengineered Tumor Tissues
Zihan Ling1, Burke Niego2, Qingyang Li1
1Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, 15213, USA.
Advanced Materials (Deerfield Beach, Fla.)
|September 6, 2025
Summary
This study introduces a new method to detect newly synthesized extracellular matrix (newsECM) in engineered tissues. This advanced technique reveals how tumor cells remodel their environment, offering insights into tissue engineering and cancer biology.
Area of Science:
- Biomaterials Science
- Proteomics
- Tissue Engineering
Background:
- The extracellular matrix (ECM) is crucial for tissue function and cellular behavior.
- Understanding cell-ECM interactions is vital for tissue engineering but challenging due to limitations in detecting newly synthesized ECM (newsECM).
- Conventional proteomics lacks the sensitivity to capture low-abundance newsECM.
Purpose of the Study:
- To develop a sensitive and specific method for labeling, enriching, and characterizing newsECM.
- To investigate ECM synthesis patterns in bioengineered tumor models.
- To elucidate the role of decellularized ECM (dECM) scaffolds in modulating tumor cell behavior.
Main Methods:
- A glycosylation-enabled, chemoselective strategy was developed for newsECM labeling and enrichment.
- newsECM profiling was applied to bioengineered tumor tissues (dECM-tumor and tumoroids).
- Proteomic analysis was used to compare ECM synthesis in different engineered tissue models.
Main Results:
- Distinct ECM synthesis patterns were identified in dECM-tumor models compared to ECM-free tumoroids.
- Tumor cells in dECM scaffolds exhibited increased ECM remodeling, including ECM digestion and synthesis of tumor-associated components.
- The new newsECM profiling method demonstrated higher sensitivity than bulk proteomics for detecting remodeling events.
Conclusions:
- The developed newsECM profiling technique offers enhanced specificity and sensitivity for studying cell-ECM crosstalk.
- Decellularized ECM scaffolds promote native-like tumor cell behaviors, including significant ECM remodeling.
- This approach is valuable for understanding pathophysiological processes and advancing tissue engineering.
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