Publications by authors named "Michael Keeling"

Nano-indentation techniques might be better equipped to assess the heterogeneous material properties of plaques than macroscopic methods but there are no bespoke protocols for this kind of material testing for coronary arteries. Therefore, we developed a measurement protocol to extract mechanical properties from healthy and atherosclerotic coronary artery tissue sections. Young's modulus was derived from force-indentation data.

View Article and Find Full Text PDF

Pluripotent cells are subject to much interest as a source of differentiated cellular material for research models, regenerative medical therapies and novel applications such as lab-cultured meat. Greater understanding of the pluripotent state and control over its differentiation is therefore desirable. The role of biomechanical properties in directing cell fate and cell behavior has been increasingly well described in recent years.

View Article and Find Full Text PDF

The resistance of cancer cell subpopulations, including cancer stem cell (CSC) populations, to apoptosis-inducing chemotherapeutic agents is a key barrier to improved outcomes for cancer patients. The cationic amphiphilic drug hexamethylene amiloride (HMA) has been previously demonstrated to efficiently kill bulk breast cancer cells independent of tumor subtype or species but acts poorly toward non-transformed cells derived from multiple tissues. Here, we demonstrate that HMA is similarly cytotoxic toward breast CSC-related subpopulations that are resistant to conventional chemotherapeutic agents, but poorly cytotoxic toward normal mammary stem cells.

View Article and Find Full Text PDF

Introduction: Potential impacts of climate change on health are increasingly studied due to the diversity of the associated risks (heatwaves, air pollution, water- and vector-borne diseases). Consequently, adaptation and mitigation strategies, including tools, have been developed by different cities, states, and organizations to assess the effects of climate change on health.

Objective: Health impact assessment (HIA) is a tool that could be used to assess the potential health impacts of climate change policies before their implementation.

View Article and Find Full Text PDF

Climate change represents a serious threat to the health and well-being of populations. Today, many countries, regions, and cities around the world are implementing policies and strategies to adapt to climate change and mitigate its effects. A scoping review was performed to identify tools and methods that help integrate health into climate change adaptation and mitigation policies and strategies.

View Article and Find Full Text PDF

The keratin network of intermediate filaments provides keratinocytes with essential mechanical strength and resilience, but the contribution to mechanosensing remains poorly understood. Here, we investigated the role of the keratin cytoskeleton in the response to altered matrix rigidity. We found that keratinocytes adapted to increasing matrix stiffness by forming a rigid, interconnected network of keratin bundles, in conjunction with F-actin stress fiber formation and increased cell stiffness.

View Article and Find Full Text PDF

The mechanical state of cells is a critical part of their healthy functioning and it is controlled primarily by cytoskeletal networks (actin, microtubules and intermediate filaments). Drug-based strategies targeting the assembly of a given cytoskeletal network are often used to pinpoint their role in cellular function. Unlike actin and microtubules, there has been limited interest in the role of intermediate filaments, and fewer drugs have thus been identified and characterised as modulators of its assembly.

View Article and Find Full Text PDF

Ezrin, a member of the ERM (ezrin/radixin/moesin) family of proteins, serves as a crosslinker between the plasma membrane and the actin cytoskeleton. By doing so, it provides structural links to strengthen the connection between the cell cortex and the plasma membrane, acting also as a signal transducer in multiple pathways during migration, proliferation, and endocytosis. In this study, we investigated the role of ezrin phosphorylation and its intracellular localization on cell motility, cytoskeleton organization, and cell stiffness, using fluorescence live-cell imaging, image quantification, and atomic force microscopy (AFM).

View Article and Find Full Text PDF

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

View Article and Find Full Text PDF

Live-imaging techniques are at the forefront of biology research to explore behaviour and function from sub-cellular to whole organism scales. These methods rely on intracellular fluorescent probes to label specific proteins, which are commonly assumed to only introduce artefacts at concentrations far-exceeding routine use. Lifeact, a small peptide with affinity for actin microfilaments has become a gold standard in live cell imaging of the cytoskeleton.

View Article and Find Full Text PDF

The regulation of nuclear state by the cytoskeleton is an important part of cellular function. Actomyosin stress fibres, microtubules and intermediate filaments have distinct and complementary roles in integrating the nucleus into its environment and influencing its mechanical state. However, the interconnectedness of cytoskeletal networks makes it difficult to dissect their individual effects on the nucleus.

View Article and Find Full Text PDF