Mechanobiology

URL study guide

Description

• • Introduction to the mechanical function of subcellular constituents.
  • The cell conceived as an active mechanical machine.
  • Mechanosensing, mechanotransduction and mechanoresponse: cellular mechanoreciprocity and mechanoadaptation.

• • Overview of the physical modes of cell migration in 2D and 3D (mesenchymal ↔ amoeboid) and taxis.
  • Quantitative cell kinematics; cellular force generation and transmission; quasi-static force balance.
  • Overview of the material properties of cells – the cell as a material.

• • Cells as building blocks of simple tissues (prototissues): cell aggregates, open and closed sheets.
  • Introduction to tissue mechanics: cell collective confinement, migration and taxis; cell neighbour exchange; tissue architecture, shape and function emergence/loss.
  • Fundamentals of active nematics & topological defects in epithelial monolayers.
  • Jamming–unjamming transitions.

• • Overview of techniques to quantify cell and tissue mechanics (kinematics, dynamics and material properties).
  • Kinematics: simple metrics of individual and collective cell migration; kymographs
  • Dynamics: fundamentals of Traction Force Microscopy, Micropillars, Monolayer Stress Microscopy. Geometric Force Inference.
  • Rheology: fundamentals of Atomic Force Microscopy vs Optical Stretcher.

• • State variables and physical mechanisms.
  • In vitro vs in silico modelling across scales; categories of in silico models (single- vs multi-scale; discrete vs continuum); model components, assumptions and validation.

• • Determining the physical mechanisms of epithelial gap closure in vitro.
  • In silico discrete model for validation and prediction of physical mechanisms of gap closure.

Objectives

• Remember. Recall key definitions, symbols, units and typical orders of magnitude for mechanobiological quantities across subcellular, cellular and supracellular scales.
• Understand. Explain the cell as an active mechanical system composed of subcellular engines and structures.
• Apply. Use appropriate methods to quantify mechanobiological quantities across scales (subcellular, single-cell, cell collectives, and individual cells within collectives) reporting units, calibration, uncertainty and detection limits.
• Analyse. Characterise simple tissues as mechanically interacting ensembles of cells, linking individual cell mechanics to emergent collective mechanobiological behaviour.
• Analyse. Compare techniques for mechanical quantification in biology and select suitable methods for a given question, sample and scale.
• Evaluate. Weigh how mechanics of individual cells and cellular collectives influence behaviour, architecture, shaping and function at higher tissue or organ(ism) scales via mechano-sensing, mechano-transduction and mechano-response.
• Analyse/Evaluate. Assess the applicability, assumptions and parameterisation of in silico mechanobiology models and justify their use across subcellular, cellular and supracellular scales.
• Evaluate. Critically appraise mechanobiological data at and across subcellular cellular and supracellular scales to identify patterns or trends and their meaning; apply this knowledge to analyse and solve related problems.
• Create. Develop a slide deck and deliver a clear, well-structured oral presentation supported by concise slides to communicate and defend mechanobiology concepts and results.

Method of Assessment