Characterising the mechanical properties of haematopoietic and mesenchymal stem cells using micromanipulation and atomic force microscopy. (November 2019)

• Record Type: Journal Article
• Authors: Du, Mingming; Kavanagh, Dean; Kalia, Neena; Zhang, Zhibing
• Is Part Of: Medical engineering & physics. Volume 73(2019)
• Page Start: 18
• Page End: 29
• Publication Date: 2019-11
• Subjects: Haematopoietic stem cells -- Mesenchymal stem cells -- Deformability -- Micromanipulation -- Atomic force microscopy -- Young's modulus; Biomedical engineering -- Periodicals; Biomedical Engineering -- Periodicals; Physics -- Periodicals; Génie biomédical -- Périodiques; Biomedical engineering; Electronic journals; Periodicals; 610.28
• DOI: 10.1016/j.medengphy.2019.07.013
• Languages: English
• ISSNs: 1350-4533

Abstract

Highlights: Micromanipulation and AFM are able to quantify the mechanical properties of whole stem cells and cell membrane respectively. Mechanical distinctions exist amongst different therapeutic stem cells. SDF-1ɑ or H2 O2 pre-treatment can alter haematopoietic stem cells'SCs' deformability significantly. The study indicates that cell deformability may act as a label-free marker in cell sorting system. Abstract: Background: Improving stem cell (SC) deformability using pre-treatment strategies, or isolating more deformable sub-populations, may prevent non-specific entrapment of injected cells, maintain circulating numbers and thus increase the likelihood of capture by microvessels in injured organs. However, nothing is currently known about the basic mechanical properties of SCs, particularly with regards their elastic characteristics. This study therefore aimed to determine the mechanical characteristics of haematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) with comparisons made to neutrophils. Methods: Micromanipulation and atomic force microscopy (AFM) were used to quantitate mechanical properties following large and small deformations respectively of neutrophils, MSCs and naïve and stromal cell-derived factor-1α (SDF-1ɑ) or hydrogen peroxide (H2 O2 ) pre-treated HSCs. Results: Neutrophils and HSCs underwent rupture at ∼80% deformation. Nominal rupture stress (σR ), nominal rupture tension (TR ) and the Young's/elastic modulus at large deformations was significantly higher for neutrophils indicating they were stiffer and less deformable than HSCs. Surprisingly, MSCs did not rupture and were as deformable as HSCs despite their large size. Pre-treatment increased HSC deformability as indicated by lower rupture force, σR, TR and Young's modulus at large deformations. AFM demonstrated that pre-treatment increased the Young's modulus at smaller deformations indicating the HSC surface stiffened. This was accompanied by increased F-actin accumulation and its localisation in the cell cortex. Conclusion: This is the first study to precisely demonstrate that mechanical distinctions exist amongst different therapeutic SCs with regards their deformability and rupture response to applied stress. This can potentially be utilized as label-free markers in microfluidic cell sorting systems to separate sub-populations of potentially more therapeutic SCs.