Scaling Concepts in Serpin Polymer Physics

Materials

Vincenzo Martorana¹  Fabio Librizzi¹  Samuele Raccosta¹  Rosina Noto¹  Mauro Manno¹  AlistairM. Jagger²  DavidA. Lomas²  JamesA. Irving² 

[1]Institute of Biophysics, National Research Council of Italy, via Ugo La Malfa 153, 90146 Palermo, Italy

[2]UCL Respiratory, University College London, 5 University Street, London WC1E 6JF, UK

关键词: serpins;    serpin polymers;    atomic force microscopy;    dynamic light scattering;    conformational disease;    polymer theory;   

DOI  :  10.3390/ma14102577

来源: DOAJ

【 摘 要 】

${\alpha }_1$-Antitrypsin is a protease inhibitor belonging to the serpin family. Serpin polymerisation is at the core of a class of genetic conformational diseases called serpinopathies. These polymers are known to be unbranched, flexible, and heterogeneous in size with a beads-on-a-string appearance viewed by negative stain electron microscopy. Here, we use atomic force microscopy and time-lapse dynamic light scattering to measure polymer size and shape for wild-type (M) and Glu342→Lys (Z) ${\alpha }_1$-antitrypsin, the most common variant that leads to severe pathological deficiency. Our data for small polymers deposited onto mica and in solution reveal a power law relation between the polymer size, namely the end-to-end distance or the hydrodynamic radius, and the polymer mass, proportional to the contour length. We use the scaling concepts of polymer physics to assess that ${\alpha }_1$-antitrypsin polymers are random linear chains with a low persistence length.

【 授权许可】

Unknown