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 (H2O2) 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.
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 (H2O2) 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.
| Original language | English |
|---|---|
| Pages (from-to) | 18-29 |
| Number of pages | 12 |
| Journal | Medical Engineering & Physics |
| Volume | 73 |
| Early online date | 9 Aug 2019 |
| DOIs | |
| Publication status | Published - 1 Nov 2019 |
Keywords
- haematopoietic stem cells
- mesenchymal stem cells
- deformability
- micromanipulation
- atomic force microscopy
- Young's modulus