Liheng Cai

About

My lab’s research lies at the interface of soft (bio)materials and biology. We seek to understand and control the interactions between soft (bio)materials and living systems to solve challenges in sustainability and health. We achieve this through a combination of experimental and theoretical approaches. Our core expertise includes polymers and soft matter, biomaterials, voxelated bioprinting, and additive manufacturing of soft and inorganic matter. Our research program is highly collaborative and interdisciplinary. The philosophy of our research is to identify and solve problems of both fundamental importance and practical value; this is often accomplished by working closely with experts from various fields.

Currently, we are pursuing research in three fields: (1) polymers and soft matter, (2) advanced (bio)manufacturing, and (3) bioengineering, each of which integrates synthesis, theory, experiment, and translation. In addition to practical applications in sustainability and biomedicine, we hope to answer three grand scientific questions: 

1. What are the molecular mechanisms for nonlinear (mechanical, electric, magnetic, and optical) properties of soft materials under large deformations?
2. How do soft (bio)materials interact with biological objects?
3. Can we use polymer physics and soft matter principles to understand the rules of life? 

Polymers and soft matter

Conventional polymeric materials are made of flexible linear polymers. However, this simple molecular architecture intrinsically limits the ability of using linear polymers to create soft materials with nonlinear mechanical, biophysical, and biochemical complexities for diverse practical applications. Unlike conventional linear polymers, a bottlebrush polymer has a long linear backbone densely grafted by many relatively short linear side chains. Yet, analogous to sausage, as opposed to spaghetti, a bottlebrush polymer is essentially a type of ‘fat’ linear polymer. Further, constituent side chains can be functionalized to enable tissue-specific biochemical properties without impairing the physical properties of the bottlebrush polymer. Thus, the unique molecular architecture enables bottlebrush polymers as a platform for modular soft (bio)materials design. We are researching in two directions:

1. Foldable bottlebrush polymers and networks. We are among the first to demonstrate that entanglements can be eliminated using bottlebrush polymers, enabling extremely soft, solvent-free elastomers with stiffness matching that of a wide range of biological tissues. Recently, we discovered foldable bottlebrush polymers, which feature a collapsed backbone grafted with many linear side chains. Upon elongation, the collapsed backbone unfolds to release stored length, enabling remarkable extensibility. By contrast, the network elastic modulus is inversely proportional to network strand mass and is determined by the side chains. Thus, using foldable bottlebrush polymers provide a universal strategy to decouple the stiffness and extensibility of single-network elastomers, the basic component of all kinds of polymer networks. We continue to establish the foundational science of foldable bottlebrush polymers and networks. Exploiting foldable bottlebrush polymers as a new platform, we are developing modular soft materials for additive manufacturing, extracellular matrix (ECM) mimicking biomaterials for tissue engineering, and molecular architecture encoded nanocarriers for therapeutic delivery. 
2. Associative polymers. An associative polymer carries many stickers that can form reversible bonds. Unlike permanent covalent bonds, a reversible association can break and reform at laboratory timescales. This process not only slows down polymer dynamics but also dissipates energy, enabling macroscopic properties inaccessible by conventional polymers. As a result, associative polymers provide solutions to some of the most pressing challenges in sustainability and health. For more than 30 years, the understanding is that reversible associations change the shape of linear viscoelastic spectra by adding a plateau in the intermediate frequency range, at which associations have not yet relaxed and thus effectively act as crosslinks. Recently, my lab showed that this classic molecular picture is incomplete for homogeneous associative polymers carrying high fractions of stickers. We discover show that the fraction of stickers, in addition to the conventionally thought sticker-sticker binding energy, is another dominant parameter controlling the dynamics of associative polymers without microphase separation. Built on this breakthrough, we are answering how the distribution, density, and strength of associations determine the dynamics and glass transition of associative polymers. In parallel, we are exploiting the obtained knowledge to innovate supramolecular materials for sustainability and tissue engineering. 

Advanced (bio)manufacturing

1. Additive manufacturing of soft/inorganic matter. Existing polymers for 3D printing are largely limited to stiff plastics. We develop new design principles to create 3D printable soft materials. Integrating polymer chemistry, polymer physics, molecular theory, and multi-scale modeling, we are establishing molecule-structure-property-function relations for new classes of adaptive soft materials. By developing various kinds of 3D printing techniques, we transform these materials to multi-material, functional organic/inorganic architectures for applications including soft robots and high-performance catalysis.
2. Voxelated bioprinting. Inspired by Minecraft®, a popular video game that uses individual 3D cubes as voxels to create a virtual world, our lab has proposed and proved the concept of voxelated bioprinting, a technology that enables the Digital Assembly of Spherical bio-ink Particles (DASP). DASP enables on-demand generation, deposition, and assembly of highly viscoelastic bio-ink voxels in an aqueous environment. Using DASP, we assemble cell encapsulated droplets to create highly functional 3D tissue mimics with prescribed cell-matrix and cell-cell interactions. Research along this direction includes: (1) development of voxelated bioprinting platform, (2) design and synthesis of modular biomaterials, and (3) engineering tissue mimics for basic and translational biomedicine. 

Bioengineering

1. Human lung defense. As we are alive, we must breathe. This process of breathing brings bacterial, viral, and environmental particulates into our lungs. How can the lungs fight against them? To answer this question, we have developed micro-human airway device to capture the geometric and biological features of human airway and exploit this device to study human lung defense. Integrating soft matter physics, engineering, molecular biology, bioinformatics, and systems biology, we are investigating the interactions between mucus and three indispensable components of the microenvironment: cilia, cells, and bacteria.
2. Mucosal delivery. The mucus is a viscoelastic hydrogel that lines the epithelial surface in our respiratory, gastrointestinal, and genitourinary tracts. The sticky mucus represents the first line of defense by trapping any external objects. However, the mucus also prevents the delivery of therapeutic agents to the mucosal surface. Further, the epithelium, connected by tight junctions, presents an additional barrier to therapeutic delivery. Our lab has discovered a new way to solve this challenge by exploiting polyethylene glycol (PEG) bottlebrush polymers as nanocarriers for mucosal delivery. The flexible, worm-like PEG bottlebrush sneaks through the tight mucus network mesh to cross the membrane of epithelial cells via bottlebrush architecture enhanced endocytosis. We are exploiting PEG bottlebrush nanocarriers to deliver small molecular drugs and therapeutic peptides/proteins to treat chronic bronchitis and for therapeutic delivery to the intestine.

Education

B.S. Physics, Lanzhou University, 2006

Ph.D. Materials Science, University of North Carolina at Chapel Hill, 2012

Postdoctoral Fellow, Harvard University, 2013-2017