| Autor: |
Cho KR; Bioscience and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550, United States.; The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.; Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 31116, Chungnam, Republic of Korea.; Department of Chemical and Biological Engineering, College of Engineering, Sookmyung Women's University, Seoul 04310, Republic of Korea., Lee JH; Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 31116, Chungnam, Republic of Korea., Seo HS; School of Naval Architecture Engineering and Ocean Engineering, University of Ulsan, Ulsan 44610, Republic of Korea., Ji Y; Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 31116, Chungnam, Republic of Korea., Park JH; Andlinger Center for Energy and the Environment, and Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, United States., Lee SE; Department of Mechanical Engineering, Inha University, Incheon 22212, Republic of Korea., Kim HW; Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 31116, Chungnam, Republic of Korea., Wu KJJ; Bioscience and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550, United States., Kulshreshtha P; The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States. |
| Abstrakt: |
Calcium oxalate monohydrate (COM) crystal is the most common crystalline component of human kidney stones. The molecular-scale inhibitory mechanisms of COM crystal growth by urinary biomolecules such as citrate and osteopontin adsorbed onto the crystal surface are now well understood. However, the pathways by which dissolved calcium and oxalate ions are incorporated into the molecular step of the COM crystal surface, leading to COM crystal growth-a prerequisite to be elucidated for developing effective therapeutics to inhibit COM stones-remain unknown. Here, using in situ liquid-phase atomic microscopy along with a step kinetic model, we reveal the pathways of the calcium and oxalate ions into the COM molecular step via the growth speed analysis of the molecular steps with respect to their step width at the nanoscale. Our results show that, primarily, the ions are adsorbed onto the terrace of the crystal surface from the solution-the rate-controlling stage for the molecular step growth, i.e., COM crystal growth-and then diffuse over it and are eventually incorporated into the steps. This primary pathway of the ions is unaffected by the model peptide D-Asp 6 adsorbed on the COM crystal surface, suggesting that urinary biomolecules will not alter the pathway. These new findings rendering an essential understanding of the fundamental growth mechanism of COM crystal at the nanoscale provide crucial insights beneficial to the development of effective therapeutics for COM kidney stones. |
