Both biological and engineering approaches have contributed significantly to the recent advance in the field of mechanobiology.Collaborating with biologists,bio-engineers and materials scientists have employed the techniques stemming from the conventional semiconductor industry to rebuild cellular milieus that mimic critical aspects of in vivo conditions and elicit cell/tissue responses in vitro.Such reductionist approaches have help to unveil important mechanosensing mechanism in both cellular and tissue level,including stem cell differentiation and proliferation,tissue expansion,wound healing,and cancer metastasis.In this mini-review,we discuss various microfabrication methods that have been applied to generate specific properties and functions of designer substrates/devices,which disclose cell-microenvironment interactions and the underlying biological mechanisms.In brief,we emphasize on the studies of cell/tissue mechanical responses to substrate adhesiveness,stiffness,topography,and shear flow.Moreover,we comment on the new concepts of measurement and paradigms for investigations of biological mechanotransductions that are yet to emerge due to on-going interdisciplinary efforts in the fields of mechanobiology and microengineering.