| Summary: | Mechanical interlocking is a prominent phenomenon both in macroscopic objects and in microscopic molecules. Not only is it aesthetically appealing, it also leads to unique properties such as extraordinary mechanical stability. This review focuses on mechanically interlocked biomacromolecules. After a brief clarification on the concept and scope, we discuss their classification and summarize the three main types of mechanically interlocked biomacromolecules (i.e., DNA, RNA, and proteins) in terms of their natural occurrence, synthetic methods, relevant applications, and functional benefits. It has been found that mechanical interlocking reshapes the conformational space of these chain molecules, which provides numerous opportunities to tailor their properties and create new functions. Since the development of ''assembly-reaction'' synergies has greatly facilitated their synthetic availability, these mechanically linked biomacromolecules will become unique and promising candidates for various applications in biomaterials and biomedicine.
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