Mapping the Nonreciprocal Micromechanics of Individual Cells and the Surrounding Matrix Within Living Tissues

The biomechanical properties of the extracellular matrix (ECM) play an important role in cell migration, gene expression, and differentiation. Biomechanics measurements of ECM are usually performed on cryotomed tissue sections. However, studies on cell/matrix interplay are impossible to perform due to disruptions in cell viability and tissue architecture from freeze-thaw cycling. We developed a technique to map the stiffness of living cells and surrounding matrix by atomic force microscopy and use fluorescence microscopy to relate those properties to changes in matrix and cell structure in embryonic and adult tissues in situ. Stiffness mapping revealed significant differences between vibratomed (living) and cryotomed tissues. Isolated cells are softer than those in native matrix, suggesting that cell mechanics are profoundly influenced by their three-dimensional environment and processing state. Viable tissues treated by hyaluronidase and cytochalasin D displayed targeted disruption of matrix and cytoskeletal networks, respectively. While matrix stiffness affected cellular stiffness, changes in cell mechanics did not reciprocally influence matrix stiffness

The stiffness of living tissues and its implications for tissue engineering

The past 20 years have witnessed ever- growing evidence that the mechanical properties of biological tissues, from nanoscale to macroscale dimensions, are fundamental for cellular behaviour and consequent tissue functionality. This knowledge, combined with previously known biochemical cues, has greatly advanced the field of biomaterial development, tissue engineering and regenerative medicine. It is now established that approaches to engineer biological tissues must integrate and approximate the mechanics, both static and dynamic, of native tissues. Nevertheless, the literature on the mechanical properties of biological tissues differs greatly in methodology, and the available data are widely dispersed. This Review gathers together the most important data on the stiffness of living tissues and discusses the intricacies of tissue stiffness from a materials perspective, highlighting the main challenges associated with engineering lifelike tissues and proposing a unified view of this as yet unreported topic. Emerging advances that might pave the way for the next decadeâ s take on bioengineered tissue stiffness are also presented, and differences and similarities between tissues in health and disease are discussed, along with various techniques for characterizing tissue stiffness at various dimensions from individual cells to organs.The authors would like to acknowledge financial support from the European Research Council, grant agreement ERC-2012-ADG 20120216-321266 (project ComplexiTE). C.F.G. acknowledges scholarship grant no. PD/BD/135253/2017 from Fundação para a Ciência e Tecnologia (FCT). The authors also thank the peer-reviewers for the constructive comments and suggestions that helped to shape this manuscript