PhD work

Bistablility in the synchronization of actuated microfilaments

Hanliang Guo, Lisa Fauci, Michael Shelley, Eva Kanso. submitted.

Cilia and flagella are essential building blocks for biological fluid transport and locomotion at the micron scale. They often beat in synchrony and may transition between different synchronization modes in the same cell type. Here, we investigate the behavior of elastic microfilaments, protruding from a surface and driven at their base by a configuration-dependent torque. We consider full hydrodynamic interactions among and within filaments and no slip at the surface. Isolated filaments exhibit periodic deformations, with increasing waviness and frequency as the magnitude of the driving torque increases. Two nearby but independently-driven filaments synchronize their beating in-phase or anti-phase. This synchrony arises autonomously via the interplay between hydrodynamic coupling and filament elasticity. Importantly, in-phase and anti-phase synchronization modes are bistable and co-exist for a range of driving torques and separation distances. These findings are consistent with experimental observations of in-phase and anti-phase synchronization in the biflagellate Chlamydomonas reinhardtii and could have important implications on understanding the biophysical mechanisms underlying transitions between multiple synchronization modes.

Motile cilia create fluid-mechanical microhabitats for the active recruitment of the host microbiome

Janna Nawroth, Hanliang Guo, Eric Koch, E.A. Heath-Heckman, J.C. Hermanson, Edward Ruby, John Dabiri, Eva Kanso, Margaret McFall-Ngai. PNAS 114 (36), 9510-9516 (2017).[ pdf ] [ link ]

Paper featured in PNAS In This Issue, USC News.

Our understanding of ciliary activity along mucus membranes has been principally restricted to the function of clearing particles and potential pathogens from tissue surfaces. Here we show that ciliated epithelia can create fluid-mechanical microenvironments for the active recruitment of the host microbiome. Using an established model system for investigating bacteria-host symbiosis, we develop an empirical and theoretical framework with which we conduct a census of ciliated cell types, create structural maps, and resolve the spatiotemporal flow dynamics. Our multiscale analysis revealed how distinct populations of cilia collectively generate spatially organized flow compartments that provide selective barrier and transport functions, and isolate bacterial candidates. These results reveal that ciliated epithelia express complex fluid-organization and flow behaviors, enabling a previously unrecognized potential to influence tissue remodeling, pathogen exploitation, and symbiont recruitment to specific tissues.

A Computational Study of Mucociliary transport in healthy and diseased environments

Hanliang Guo, Eva Kanso. Accepted to European Journal of Computational Mechanics. [ pdf ] [ link ]

Mucociliary clearance in the lung is the primary defense mechanism that protects the airways from inhaled toxicants and infectious agents. The system consists of a viscoelastic mucus layer on top of a nearly-viscous periciliary layer surrounding the motile cilia. In healthy environments, the thickness of the periciliary layer is comparable to the cilia length. Perturbations to this system, whether due to a genetic disorder or acquired causes, are directly linked to infection and disease. For example, depletion of the periciliary layer is typically observed in diseases such as chronic obstructive pulmonary disease and cystic fibrosis. Clinical evidence connects the periciliary layer depletion to reduced rates of mucus clearance. In this work, we develop a novel computational model to study mucociliary transport in a microfluidic channel. We systematically vary the viscoelastic properties and thickness of the mucus layer to emulate healthy and diseased environments. We assess cilia performance in terms of three metrics: flow transport, internal power expended by the cilia, and transport efficiency. We find that, compared to a control case with no mucus, a healthy mucus layer enhances cilia performance in all three metrics. That is to say, a healthy mucus layer not only improves flow transport, resulting in better clearance of harmful substances, but it does so at an energetic advantage to the cilia. Stiffer mucus enhances further the transport efficiency. In contrast, in diseased environments where the periciliary layer is depleted, mucus hinders transport and stiffer mucus leads to a substantial decrease in transport efficiency. This decrease in transport is accompanied by an increase in the internal power needed to complete the cilia beating cycle. Cilia failure would occur when the required power is higher than that afforded by the cilia internal machinery. This work provides a quantitative framework for assessing cilia performance in flow transport in healthy and diseased environments, that can be equally applied to experimental data on cilia-driven flows. It can thus provide a tool for the diagnostic of diseases related to mucociliary transport.

Evaluating efficiency and robustness in cilia design

Hanliang Guo, Eva Kanso. Phys. Rev. E, 93, 033119 (2016). [ pdf ] [ link ]

Motile cilia are used by many eukaryotic cells to transport flow. Cilia-driven flows are important to many physiological functions, yet a deep understanding of the interplay between the mechanical structure of cilia and their physiological functions in healthy and diseased conditions remains elusive. For developing such understanding, one needs a quantitative framework for assessing cilia performance and robustness when subject to perturbations in the cilia apparatus. Here, we link cilia design (beating patterns) to function (flow transport) in the context of experimentally- and theoretically-derived cilia models. We particularly examine the optimality and robustness of cilia design. Optimality refers to efficiency of flow transport, while robustness is defined as low sensitivity to variations in the design parameters. We find that suboptimal designs can be more robust than optimal ones. That is, designing for the most efficient cilium does not guarantee robustness. These findings have significant implications on the understanding of cilia design in artificial and biological systems.

Cilia beating patterns are not hydrodynamically optimal

Hanliang Guo, Janna Nawroth, Yang Ding, Eva Kanso. Phys. Fluids, 26, 091901 (2014). [ pdf ] [ link ]

We examine the hydrodynamic performance of two cilia beating patterns reconstructed from experimental data. In their respective natural systems, the two beating patterns correspond to: (A) pumping-specialized cilia, and (B) swimming-specialized cilia. We compare the performance of these two cilia beating patterns as a function of the metachronal coordination in the context of two model systems: the swimming of a ciliated cylinder and the fluid pumping by a ciliated carpet. Three performance measures are used for this comparison: (i) average swimming speed/pumping flow rate; (ii) maximum internal moments generated by the cilia; and (iii) swimming/pumping efficiencies. We found that, in both models, pattern (B) outperforms pattern (A) in almost all three measures, including hydrodynamic efficiency. These results challenge the notion that hydrodynamic efficiency dictates the cilia beating kinematics, and suggest that other biological functions and constraints play a role in explaining the wide variety of cilia beating patterns observed in biological systems.

Other work for fun

Inferring the Temporal Order of Cancer Gene Mutations in Individual Tumor Samples

Jun Guo, Hanliang Guo, Zhanyi Wang. PLoS ONE, 9(2): e89244 (2014).[ pdf ] [ link ]

The temporal order of cancer gene mutations in tumors is essential for understanding and treating the disease. Existing methods are unable to infer the order of mutations that are identified at the same time in individual tumor samples, leaving the heterogeneity of the order unknown. Here, we show that through a complex network-based approach, which is based on the newly defined statistic –carcinogenesis information conductivity (CIC), the temporal order in individual samples can be effectively inferred. The results suggest that tumor-suppressor genes might more frequently initiate the order of mutations than oncogenes, and every type of cancer might have its own unique order of mutations. The initial mutations appear to be dedicated to acquiring the function of evading apoptosis, and some order constraints might reflect potential regularities. Our approach is completely data-driven without any parameter settings and can be expected to become more effective as more data will become available.

An Activation Force-based Affinity Measure for Analyzing Complex Networks

Jun Guo, Hanliang Guo, Zhanyi Wang. Sci. Rep. 1, 113 (2011). [ pdf ] [ link ]

Affinity measure is a key factor that determines the quality of the analysis of a complex network. Here, we introduce a type of statistics, activation forces, to weight the links of a complex network and thereby develop a desired affinity measure. We show that the approach is superior in facilitating the analysis through experiments on a large-scale word network and a protein-protein interaction (PPI) network consisting of ~5,000 human proteins. The experiment on the word network verifies that the measured word affinities are highly consistent with human knowledge. Further, the experiment on the PPI network verifies the measure and presents a general method for the identification of functionally similar proteins based on PPIs. Most strikingly, we find an affinity network that compactly connects the cancer-associated proteins to each other, which may reveal novel information for cancer study; this includes likely protein interactions and key proteins in cancer-related signal transduction pathways.

Popular science

The math behind microbot locomotion

My poster describing math behind microbot locomotion is featured in SIAM's Math Matters, Apply it! competition.

Math Matters, Apply It! is an applied mathematics awareness campaign, created for anyone who wants to know more about the mathematics behind everyday life and the technologies we encounter.


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