Physical properties such as tissue stiffness have been shown to influence stem cell fate in vitro. It is possible that spatiotemporal changes in stiffness may influence tissue formation during development; however, it has been difficult to analyse this due to the technical limitations of measuring stiffness in embryonic tissues. In this issue (p. 3793), Yoichi Kosodo and colleagues overcome this problem and provide a novel approach to measuring changes in stiffness using atomic force microscopy combined with immunostaining in the embryonic mouse cerebral cortex during development. By combining these two techniques, the authors show that all layers in the developing cortex undergo significant changes in stiffness throughout the embryonic stages. In the ventricular and subventricular zones, stiffness gradually increases throughout development, while the intermediate zone and cortical plate show an initial increase in stiffness followed by a decrease before birth. Deconstruction of the role of cell and matrix in modulating stiffness in the developing brain reveals that tissue stiffness cannot be solely determined by the stiffness of the cells that constitute the tissue. This study not only sheds light on the spatiotemporal dynamics of stiffness in the developing mouse brain, but also provides a possible approach for understanding the global profile of physical properties in other developing organs.