Recapitulating the Cell-Niche Biomechanics at the Macro and Micro Scales

Udi Sarig ¹ Hadar Sarig ¹ Muthu Kumar Krishnamoorthi muthukum003@e.ntu.edu.sg ^1,4 Aleksander Gora ² Gigi Chi Ting Au-Yeung ¹ Elio De Berardinis ¹ Su Yin Chaw ¹ Hanumakumar Bogireddi ¹ Eyal Zussman ^2,3 Seeram Ramakrishna ² Tan Lay Poh ¹ Freddy Boey Yin Chiang ¹ Subbu S. Venkatraman ¹ Marcelle Machluf ^1,4

¹School of Materials Science & Engineering, Nanyang Technological University, Singapore, Singapore
²Department of Mechanical Engineering, National University of Singapore, Singapore, Singapore
³Faculty of Mechanical Engineering, Technion-Israel Institute of Technology, Israel, Israel
⁴Faculty of Biotechnology & Food Engineering, Technion-Israel Institute of Technology, Israel, Israel

Biomechanical perception of tissue generation during development, regeneration following injury or de novo tissue engineering in vitro, is based on the collective, average macro-scale values to characterize reciprocal cellular interactions with their microenvironment (i.e., niche). These average values overlook the specific interaction levels of the extracellular matrix (ECM) with different cell types and their local contribution to tissue formation, integration, and maturation. Here we show that depending on the relative presence of different cell types and their ratio to that of extracellular matrix (ECM), different biomechanical outcomes can be expected. We developed a unique model system to study such interactions using atomic force microscopy (AFM) under defined in vitro conditions revealing cell-type dependent interactions, synergistic effect of co-cultures to tissue integration, and newly suggested quantifiable measures as indicators of tissue assembly and maturation processes. This work may benefit basic and translational research in developmental biology, tissue engineering, regenerative medicine and cancer biomechanics.