Defence Ishu Aggarwal: "Computational analysis of sensing and actuation in natural and nature-inspired ciliary systems"

Promotors: 1^st promotor: Prof Patrick Onck, 2^nd promotor: Prof Ajay Kottapalli

Abstract: The ability to sense and respond to environmental stimuli is a fundamental characteristic of life, determining the survival, adaptation, and functional complexity across organisms—from unicellular protozoa to complex vertebrates. These bidirectional organism-environment interactions rely on finely tuned biological systems for essential processes such as navigation, communication, reproduction, and homeostasis. Many of these are controlled by microscopic, hair-like organelles known as cilia. Depending on their function, cilia are broadly categorized as motile (responsible for generating fluid flow) or sensory (transducing mechanical stimuli into electrical responses). They display diverse morphologies tailored to specific physiological roles. Despite their ubiquity and importance, key questions remain regarding their mechanobiology and morphological diversity, including the mechanisms of left-right symmetry breaking in vertebrate embryos, the unique morphology of stereocilia hair bundles, and the functional significance of morphological variation in fish neuromast cupulae, dome-shaped structures capping hair bundles.

This thesis provides insights into the physical mechanisms and the influence of critical structural parameters that govern the performance of natural ciliary systems through simulations of cilia–fluid interactions using finite element method-based models. The first part investigates the artificial embryonic node to explore hypothesized mechanical and biochemical mechanisms by which motile cilia-generated flows are sensed during the establishment of embryonic left-right asymmetry. The second part focuses on understanding the form-function relationships of mechanosensory cilia. Simulations of stereocilia hair bundles in the bullfrog saccule elucidate how their morphology enables exceptional mechanical sensitivity, robustness, and reliability. Similarly, computational models of fish neuromast cupulae demonstrate that variations in their geometry, material properties, and spatial arrangement significantly modulate their sensitivity to external hydrodynamic stimuli.

The final part of the thesis presents a bioinspired microfluidic design for efficient mixing in stagnant fluids using inclined artificial cilia composed of partially magnetic and nonmagnetic soft polymers. The mixing performance of this system is evaluated under varying geometric and actuation parameters. The thesis concludes by combining all findings on these (biological and artificial) ciliary systems and their outlook, where developing sensitive and reliable micro/nanoscaled stereocilia hair bundle and fish cupula-inspired flow sensors could significantly contribute to biomedical technologies, diagnostics, and industrial applications.

Dissertation