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Updated: Aug 14, 2026

In vitro Synthesis of Native, Fibrous Long Spacing and Segmental Long Spacing Collagen
Published on: September 20, 2012
Liquid Transmission Electron Microscopy for Probing Collagen Biomineralization
Liza-Anastasia DiCecco1,2, Ruixin Gao3, Jennifer L Gray4
1Department of Materials Science and Engineering, McMaster University, Hamilton, ON L8S 4L8, Canada.
Abstract:
Collagen biomineralization is fundamental to hard tissue assembly. While studied extensively, collagen mineralization processes are not fully understood, with the majority of theories derived from electron microscopy (EM) under static, dehydrated, or frozen conditions, unlike the liquid phase environment where mineralization occurs. Herein, novel liquid transmission EM (TEM) strategies are presented, in which collagen mineralization was explored in liquid for the first time via TEM. Custom thin-film enclosures were employed to visualize the mineralization of reconstituted collagen fibrils in a calcium phosphate and polyaspartic acid solution to promote intrafibrillar mineralization. TEM highlighted that at early time points precursor mineral particles attached to collagen and progressed to crystalline mineral platelets aligned with fibrils at later time points. This aligns with observations from other techniques and validates the liquid TEM approach. This work provides a new liquid imaging approach for exploring collagen biomineralization, advancing toward understanding disease pathogenesis and remineralization strategies for hard tissues.
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