Morphogenesis is one of the grand challenges in biology. Shape arises because cells change in number, size, shape, and movement; understanding how this actually happens and how it is controlled is a natural goal. Our work forms a small rivulet off the main stream that aims to quantifies the ideas espoused by the early pioneers of developmental biology such as Roux, His, and D’Arcy Thompson (read an essay from Development on the centenary of “On growth and form”) and has led to a deeper appreciation of the role of physics in organogenesis in the context of how we should describe it, how we may predict it, and finally, how we may control it.
To correctly quantify the geometry of tissue morphogenesis, we have developed geometrical approaches to tissue tectonics using invariants based on velocity gradients to characterize and compare dynamic fate maps of multi-cellular tissues, borrowing ideas from hydrodynamics. This approach allows one to distinguish the change in tissue shape because of the relative magnitudes of cell shape changes and cell movements, with many experimental implications for robustness in developing tissues (e.g. in convergent extension, etc.). More recently, we have used ideas from nonlinear dynamics to characterize properly invariant measures of deformation that describe the dynamic morphoskeletons – the organizers of large scale cell movements in multicellular tissues. A recent outcome has been to complement this with direct measurements of the forces associated with morphing tissues.
Moving towards a predictive theory for how genes link to geometry, we have explored the physical basis of morphogenesis in plants and animals in a variety of examples – from fungi to flowers, from the vertebrate gut to the mammalian brain. For example, inspired by observations from our experimental colleagues, we provided a theoretical basis for the evolution of multicellular tissue organization in choanoflagellates, likely the closest eukaryotic relatives of metazoans using simple, testable geometrical and biophysical principles.
We have also worked on understanding the form of plant organs, such as leaves and flowers, treated as mathematical problems of how to embed non-Euclidean surface metrics in three-dimensional space – in such contexts as the shape of a leaf, the blooming of a flower and the elongation of Columbine petal spurs using cell shape change- and understanding the recent evolutionary radiation of this species. We have also shown how slow movements of water can lead to morphological changes in such instances as the opening and closing of a pine cone or the coiling and overwinding of tendrils, explaining observations going back to Darwin’s work on the power of movement in plants.
In the study of morphogenesis in animals, we suggested that hydraulics could play an important role in guiding and informing the dynamics of cystic organoids, and followed this with studies of embryo size and cell fate control during the early developmental stages of mammalian embryos, and in the size control of the inner ear in fishes. By quantifying the concept of differential growth, first elucidated by D’Arcy Thompson, we have explained the growth and form of the coiled vertebrate gut with scaling ideas, results corroborated using our own biophysical experiments and those done by our collaborators across multiple species. This idea also allowed us to explain villification, the formation of protrusions responsible for nutrient absorption in the intestine, and our study linking experiments and computations explains the process in a growing organism and across species. We have also studied the geometrical and physical basis for differential gene expression during villi formation, the genetic underpinnings of gut coiling and more recently, the active mechanics of gut elongation.
When combined with our study of sulcification, whereby sharp creases form on the surface of soft solids, we have been able to explain the gyrification of the mammalian brain that has a cortex that grows but is constrained by the underlying white matter. Our experiments using a humble swelling gel along with a computational model shows that we can recapitulate the basic folding patterns in the human fetal brain, and also construct a gyrification morphospace for the patterns seen across species in terms of two geometric parameters that correspond to the relative thickness of the cortex and the relative growth of the cortex.
Differential growth is but one of many principles associated with patterning in living systems. We have also explored the role of differential motility and contractility from a theoretical perspective, and are currently working to see how these principles might also be relevant to understanding the elongation of the body and the patterning processing associated with somitogenesis.
M. Lewicka, L. Mahadevan, M. R. Pakzad, Ann. I. H. Poincare - AN , 2015. [View PDF] [Download PDF]
C.J. Chan, M. Costanzo, T. Ruiz-Herrero, G. Monke, R. Petrie, L. Mahadevan, T. Hiiragi, Nature 571, 112–116, 2019. [DOI] [View PDF] [Download PDF]