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Open Access Highly Accessed Research article

Stringent requirement for spatial arrangement of extracellular matrix in supporting cell morphogenesis and differentiation

Sze Wing Tang1, Wing Yin Tong1, Wei Shen12, Kelvin W K Yeung23* and Yun Wah Lam1*

Author Affiliations

1 Department of Biology & Chemistry, City University of Hong Kong, Hong Kong, China

2 Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong, China

3 Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, The University of Hong Kong Shenzhen Hospital, 1 Haiyuan 1st Road, Futian Distract, Shenzhen, China

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BMC Cell Biology 2014, 15:10  doi:10.1186/1471-2121-15-10

Published: 25 March 2014



In vitro experiments on the functional roles of extracellular matrix (ECM) components usually involve the culture of cells on surfaces coated with purified ECM components. These experiments can seldom recuperate the spatial arrangement of ECM found in vivo. In this study, we have overcome this obstacle by using histological sections of bovine Achilles tendon as cell culture substrates.


We found that tendon sections can be viewed as a pre-formed block of ECM in which the collagen fibrils exhibited a spatial regularity unraveled in any artificially constructed scaffold. By carving the tendon at different angles relative to its main axis, we created different surfaces with distinct spatial arrangements of collagen fibrils. To assess the cellular responses to these surfaces, human mesenchymal stem cells (MSCs) were directly cultured on these sections, hence exposed to the collagen with different spatial orientations. Cells seeded on longitudinal tendon sections adopted a highly elongated and aligned morphology, and expressed an increased level of tenomodulin, suggesting that the collagen fibrils present in this section provide a microenvironment that facilitates cell morphogenesis and differentiation. However, MSC elongation, alignment and induction of tenomodulin diminished dramatically even as the sectioned angle changed slightly.


Our results suggest that cell functions are influenced not only by the type or concentration of ECM components, but also by the precise spatial arrangements of these molecules. The method developed in this study offers a simple and robust way for the studying of cell-ECM interactions, and opens many research avenues in the field of matrix biology.

Achilles tendon; Mesenchymal stem cells; Extracellular matrix; Collagen; Microenvironment