Sun Rui, Yin Zhuping, Stevens Molly M, Li Mei, Mann Stephen
Centre for Protolife Research and Centre for Organized Matter Chemistry, School of Chemistry, University of Bristol, Bristol, UK.
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Nat Commun. 2025 May 3;16(1):4138. doi: 10.1038/s41467-025-59251-x.
The fabrication of cytomimetic materials capable of orchestrated and adaptive functions remains a significant challenge in bottom-up synthetic biology. Inspired by the cell/matrix integration of living bone, here we covalently tether distributed single populations of alkaline phosphatase-containing inorganic protocells (colloidosomes) onto a crosslinked organic network to establish viscoelastic tissue-like micro-composites. The prototissues are endogenously calcified with site-specific mineralization modalities involving selective intra-protocellular calcification, matrix-specific extra-protocellular calcification or gradient calcification. To mirror the interplay between osteoblasts and osteoclasts, we prepare integrated prototissues comprising a binary population of enzymatically active colloidosomes capable of endogenous calcification and decalcification and utilize chemical inputs to induce structural remodelling. Overall, our methodology opens a route to the chemically self-regulated calcification of homogeneous and gradient tissue-like mineral-matrix composites, advances the development of bottom-up synthetic biology in chemical materials research, and could provide potential opportunities in bioinspired tissue engineering, hydrogel technologies and bone biomimetics.
制造具有协调和自适应功能的细胞模拟材料仍然是自下而上合成生物学中的一项重大挑战。受活骨细胞/基质整合的启发，我们在此将分布的单群体含碱性磷酸酶的无机原始细胞（胶体体）共价连接到交联有机网络上，以建立粘弹性组织样微复合材料。原始组织通过涉及选择性细胞内钙化、基质特异性细胞外钙化或梯度钙化的位点特异性矿化方式进行内源性钙化。为了模拟成骨细胞和破骨细胞之间的相互作用，我们制备了包含能够进行内源性钙化和脱钙的二元群体酶活性胶体体的整合原始组织，并利用化学输入诱导结构重塑。总体而言，我们的方法为均匀和梯度组织样矿物-基质复合材料的化学自调节钙化开辟了一条途径，推动了化学材料研究中自下而上合成生物学的发展，并可能在生物启发的组织工程、水凝胶技术和骨仿生学中提供潜在机会。
