Applicability of AFM to cancer-related cell changes
Professor Małgorzata Lekka, Institute of Nuclear Physics, Polish Academy of Sciences, Poland
Biomechanics-related changes have been recognised to be crucial in various pathologies. It ranges from diseases where the mechanical change is evident due to genetic modifications of cytoskeleton-membrane linkage like in muscular dystrophies to those where the alterations are only experimentally observed, eg in cancer. The determination of mechanical properties of living cells as an indicator of cancer progression has become possible with the development of such local measurement techniques as atomic force microscopy (AFM). Its most important advantage is a nanoscopic character implying that very local alterations can be quantified. In this research, AFM-derived mechanical properties of single cells and tissues have been studied in the context of cancer development. The results gathered from AFM measurements of various cancers show that, for most cancers, individual cells are characterised by the lower apparent Young’s modulus, denoting higher cell deformability. Its value depended on various factors, like the properties of substrates used for cell growth, force loading rate, or indentation depth. Despite this, the results proved the AFM capability to recognise mechanically altered cells. This can significantly impact the development of methodological approaches toward the precise identification of pathological cells. They would allow for more effective detection of cancer-related changes.
Professor Rob Ritchie FREng ForMemRS, University of California, Berkeley, USA
The structure of human cortical bone evolves over multiple length-scales from its nanoscale collagen and hydroxyapatite constituents to osteonal structures at near-millimetre dimensions. To resist fracture, bone’s toughness derives intrinsically through plasticity (fibrillar sliding) at structural-scales below a micron and extrinsically through mechanisms (crack deflection/bridging) at larger structural-scales. Biological factors, eg, ageing and bone diseases such as vitamin-D deficiency and osteogenesis imperfecta, can diminish fracture resistance over multiple length-scales by degrading both bone’s intrinsic and extrinsic toughness. The issue of bisphosphonates for treating osteoporosis will also be addressed and how these drugs can lead to atypical femoral fractures (AFFs) in a small percentage of patients who are susceptible to this drug. Bisphosphonates are excellent for treating the issue of bone quantity, but with respect to bone quality, the toughening mechanisms in bone biopsies taken from people with AFFs are clearly affected; specifically, AFFs are found to be associated intrinsically with diminished fibrillar sliding due to excessive cross-linking, and extrinsically with diminished crack deflection associated with increased, more homogenized, mineralization.
Discussion contribution – Drying of blood droplets
Professor Alex Routh, University of Cambridge, UK
When a drop of blood is placed on a solid substrate and dried a range of morphologies are observed, with many similarities to regular dried colloidal dispersions.
As with regular colloidal dispersions a front of consolidated material appears at the edge and propagates horizontally across the droplet, towards the centre. For blood, this consolidation front appears to halt a set distance from the edge and this is ascribes to gelation of the bulk fluid.
For the fully dried droplet, an accumulation of material at the edge is often observed, called a coffee ring. This edge ridge appearance is dependent on the original volume fraction of solid material as well as the drop-substrate contact angle. Theoretical predictions have been made for regular dispersions with decent agreement between theory and experiment. For blood there is considerable discrepancy in the morphological prediction which is ascribed the protein induced Marangoni flow.
Cracks are observed within the central region of the droplet, which is assumed to have gelled. The density of cracks seems to vary between patients according to their physiology.
Discussion contribution – 3D printing for orthopaedic fracture fixation
Dr Laura Leslie, Aston University, UK
Osteoporosis is a condition which causes bones to lose strength and density and can cause fragility fractures. Worldwide, around 1 in 3 women and 1 in 5 men aged over 50 will experience a fragility fracture due to osteoporosis. However, current orthopaedic screws are often poorly suited to osteoporotic bone and the design and test process for new screw designs is inhibited by the highly expensive manufacturing process and long lead time.
In this study Dr Leslie shows that the use of 3D printing can be a valid method of rapidly and cheaply producing a variety of different screw designs to test efficacy before taking those designs on for further testing.
Six different wood screws were reverse-engineered and 3D printed in polymeric resin on a Stereolithography (SLA) machine. These printed wood screws and their equivalent metal counterparts were inserted into synthetic bone blocks (Sawbones PCF5 and PCF10). Pull-out tests were conducted in accordance with ASTM 543-13. Results showed a correlation between five of the six metal vs 3D printed tests. In addition, new orthopaedic screws were designed and tested which display a greater holding power in osteoporotic bone.
Discussion contribution – Observing ice-cracks from space
Dr Oliver Marsh, British Antarctic Survey, UK
Ice shelf instability and marine ice-cliff retreat are two mechanisms that lead directly to ice loss to the ocean. The rates of fracture associated with these mechanisms are the source of the largest uncertainties in the sea level projections used to plan coastal adaptation worldwide. Cracks extending tens of kilometres across ice shelves can be mapped from space using high-resolution optical and radar satellites such as Sentinel 1 & 2 (ESA) and TerraSAR-X (DLR), providing a catalogue of observations against which to test fracture models. Here Dr Marsh shows satellite imagery of pure tensile fractures, shear fractures, buckling and branching cracks, developing on ice shelves over timescales from days to decades. They discuss the large iceberg calving events from the Brunt Ice Shelf in February 2021 and the Ronne Ice Shelf in May 2021 and the development of the fractures leading to iceberg release. Spatial heterogeneity in fracture toughness and rheology are not well constrained, but the rapidly increasing availability of satellite data provides a route to better understanding these mechanisms.