title: Quantitative nanohistological investigation of scleroderma: an atomic force microscopy-based approach to disease characterization.
abstract: Scleroderma (or systemic sclerosis, SSc) is a disease caused by excess crosslinking of collagen. The skin stiffens and becomes painful, while internally, organ function can be compromised by the less elastic collagen. Diagnosis of SSc is often only possible in advanced cases by which treatment time is limited. A more detailed analysis of SSc may provide better future treatment options and information of disease progression. Recently, the histological stain picrosirius red showing collagen register has been combined with atomic force microscopy (AFM) to study SSc. Skin from healthy individuals and SSc patients was biopsied, stained and studied using AFM. By investigating the crosslinking of collagen at a smaller hierarchical stage, the effects of SSc were more pronounced. Changes in morphology and Young's elastic modulus were observed and quantified; giving rise to a novel technique, we have termed "quantitative nanohistology". An increase in nanoscale stiffness in the collagen for SSc compared with healthy individuals was seen by a significant increase in the Young's modulus profile for the collagen. These markers of stiffer collagen in SSc are similar to the symptoms experienced by patients, giving additional hope that in the future, nanohistology using AFM can be readily applied as a clinical tool, providing detailed information of the state of collagen.
authors.affiliation: Department of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Strange
authors.affiliation: Department of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Aguayo
authors.affiliation: Department of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute.
authors.forename: Tarek
authors.initials: T
authors.lastname: Ahmed
authors.affiliation: Department of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute.
authors.forename: Nicola
authors.initials: N
authors.lastname: Mordan
authors.affiliation: Centre for Rheumatology and Connective Tissue Diseases, Royal Free Hospital, UCL Medical School.
authors.forename: Richard
authors.initials: R
authors.lastname: Stratton
authors.affiliation: UCL Eastman Dental Institute.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Porter
authors.affiliation: Department of Pediatrics, UCL Eastman Dental Institute, London, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Parekh
authors.affiliation: Department of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bozec
mesh_terms: D001706:Biopsy; D003094:Collagen / Q000648:ultrastructure; D020405:Dermis / Q000473:pathology / Q000648:ultrastructure; D055119:Elastic Modulus; D006801:Humans; D008297:Male; D018625:Microscopy, Atomic Force / Q000379:methods*; D008875:Middle Aged; D053758:Nanoparticles / Q000648:ultrastructure; D012595:Scleroderma, Systemic / Q000473:pathology*
chemical_list: D003094:Collagen
keywords: adjunct diagnosis; collagen; nanohistology; picrosirius red; rheumatology