Inflation instability in the lung: an analytical model of a thick-walled alveolus with wavy fibres under large deformations

Inflation of hollow elastic structures can become unstable and exhibit a runaway phenomenon if the tension in their walls does not rise rapidly enough with increasing volume. Biological systems avoid such inflation instability for reasons that remain poorly understood. This is best exemplified by the lung, which inflates over its functional volume range without instability. The goal of this study was to determine how the constituents of lung parenchyma determine tissue stresses that protect alveoli from instability-related overdistension during inflation. We present an analytical model of a thick-walled alveolus composed of wavy elastic fibres, and investigate its pressure–volume behaviour under large deformations. Using second-harmonic generation imaging, we found that collagen waviness follows a beta distribution. Using this distribution to fit human pressure–volume curves, we estimated collagen and elastin effective stiffnesses to be 1247 kPa and 18.3 kPa, respectively. Furthermore, we demonstrate that linearly elastic but wavy collagen fibres are sufficient to achieve inflation stability within the physiological pressure range if the alveolar thickness-to-radius ratio is greater than 0.05. Our model thus identifies the constraints on alveolar geometry and collagen waviness required for inflation stability and provides a multiscale link between alveolar pressure and stresses on fibres in healthy and diseased lungs.

Biomechanical trade-offs in the pelvic floor constrain the evolution of the human birth canal

Compared with most other primates, humans are characterized by a tight fit between the maternal birth canal and the fetal head, leading to a relatively high risk of neonatal and maternal mortality and morbidities. Obstetric selection is thought to favor a spacious birth canal, whereas the source for opposing selection is frequently assumed to relate to bipedal locomotion. Another, yet underinvestigated, hypothesis is that a more expansive birth canal suspends the soft tissue of the pelvic floor across a larger area, which is disadvantageous for continence and support of the weight of the inner organs and fetus. To test this “pelvic floor hypothesis,” we generated a finite element model of the human female pelvic floor and varied its radial size and thickness while keeping all else constant. This allowed us to study the effect of pelvic geometry on pelvic floor deflection (i.e., the amount of bending from the original position) and tissue stresses and stretches. Deflection grew disproportionately fast with increasing radial size, and stresses and stretches also increased. By contrast, an increase in thickness increased pelvic floor stiffness (i.e., the resistance to deformation), which reduced deflection but was unable to fully compensate for the effect of increasing radial size. Moreover, larger thicknesses increase the intra-abdominal pressure necessary for childbirth. Our results support the pelvic floor hypothesis and evince functional trade-offs affecting not only the size of the birth canal but also the thickness and stiffness of the pelvic floor.

Self-organized patterning of cell morphology via mechanosensitive feedback

Tissue organization is often characterized by specific patterns of cell morphology. How such patterns emerge in developing tissues is a fundamental open question. Here, we investigate the emergence of tissue-scale patterns of cell shape and mechanical tissue stress in the Drosophila wing imaginal disc during larval development. Using quantitative analysis of the cellular dynamics, we reveal a pattern of radially oriented cell rearrangements that is coupled to the buildup of tangential cell elongation. Developing a laser ablation method, we map tissue stresses and extract key parameters of tissue mechanics. We present a continuum theory showing that this pattern of cell morphology and tissue stress can arise via self-organization of a mechanical feedback that couples cell polarity to active cell rearrangements. The predictions of this model are supported by knockdown of MyoVI, a component of mechanosensitive feedback. Our work reveals a mechanism for the emergence of cellular patterns in morphogenesis.

Src kinases relax adherens junctions between the neighbors of apoptotic cells to permit apical extrusion

Apoptotic cell extrusion is predicted to accumulate local tissue stresses that represent a mechanical cost for the epithelium, but how such costs may be alleviated is poorly understood. Here we identify a Src family kinase-mechanosensitive early immediate response of neighbor cells that relieves mechanical stress and allows extrusion to occur.

Self-organized patterning of cell morphology via mechanosensitive feedback

ABSTRACTTissue organization is often characterized by specific patterns of cell morphology. How such patterns emerge in developing tissues is a fundamental open question. Here, we investigate the emergence of tissue-scale patterns of cell shape and mechanical tissue stress in the Drosophila wing imaginal disc during larval development. Using quantitative analysis of the cellular dynamics, we reveal a pattern of radially oriented cell rearrangements that is coupled to the buildup of tangential cell elongation. Developing a laser ablation method, we map tissue stresses and extract key parameters of tissue mechanics. We present a continuum theory showing that this pattern of cell morphology and tissue stress can arise via self-organization of a mechanical feedback that couples cell polarity to active cell rearrangements. The predictions of this model are supported by knockdown of MyoVI, a component of mechanosensitive feedback. Our work reveals a mechanism for the emergence of cellular patterns in morphogenesis.

Compression of limbs by tight bandages

Human body parts are sometimes compressed by tight clothes, footwear, bandages etc. Therefore, it is important to balance between functionality and comfort of garments in order to avoid negative effects on human health. Mechanical properties of both garment and tissue need to be taken into account for the analysis of pressure of tight garments. The thick walled tube theory is adjusted to a composite cylinder with a rigid core, as an approximate limb model with corresponding edge conditions. The results suggest the effect of tightness and elastic properties of the tissue and the tight garment on the level and type of tissue stresses.