Biomolecular Assemblies: Moving from Observation to Predictive Design

Abstract

Biomolecular assembly is a key driving force in nearly all life processes, providing structure, information storage, and communication within cells and at the whole organism level. These assembly processes rely on precise interactions between functional groups on nucleic acids, proteins, carbohydrates, and small molecules, and can be fine tuned to span a range of time, length, and complexity scales. Recognizing the power of these motifs, researchers have sought to emulate and engineer biomolecular assemblies in the laboratory, with goals ranging from modulating cellular function to the creation of new polymeric materials. In most cases, engineering efforts are inspired or informed by understanding the structure and properties of naturally occurring assemblies, which has in turn fueled the development of predictive models that enable computational design of novel assemblies. This Review will focus on selected examples of protein assemblies, highlighting the story arc from initial discovery of an assembly, through initial engineering attempts, toward the ultimate goal of predictive design. The aim of this Review is to highlight areas where significant progress has been made, as well as to outline remaining challenges, as solving these challenges will be the key that unlocks the full power of biomolecules for advances in technology and medicine.

Protein assembly systems in natural and synthetic biology

“…This can occur aberrantly and lead to disease; but there is also accumulating evidence that aggregation phenomena can be regulated by the cell and used to carry out important and beneficial biological functions ranging from molecular scaffolding to memory [1][2][3][4]. Moreover, when designing synthetic cellular systems using synthetic biology, we argue that protein aggregation may be viewed as a "feature" rather than a "bug", and that self-assembling elements possess unique properties that can be exploited to engineer new biological functions [5]. In this Review, we provide a brief introduction to protein assembly and the spectrum of aggregation phenomena found in nature, we survey the diverse and rapidly expanding set of biological functions driven by supramolecular assemblies, and finally we offer a prospective discussion of the methods and benefits of their purposeful manipulation in cells and organisms.…”

Engineering Hydrogels beyond a Hydrated Network

“…However, the utility of DoE in the screening of large synthetic combinatorial biomaterial library remains to be established. Moving from observation to predictive design represents another trend in biomaterials research . In the era of artificial intelligence (AI), machine learning techniques can offer many tools to make predictions about cell–material interactions .…”

“…In summary, through identifying and optimizing a few most critical parameters, e.g., the gradual stiffness change for intestinal stem cell differentiation, the fine‐tuning of sulfation degree in wound dressing to facilitate wound healing, or the presence of heparan sulfate to direct the differentiation of neuronal stem cells, biomaterials can be specifically tailored to support the survival, growth, and differentiation of specific cells types . Since defined parameter are easier to feed into simulations, reducing the complex biological microenvironments to chemically defined synthetic matrices helps to model materials for various stem cell niches and to meet key requirements for regenerative medicine and cell replacement therapy . “Everything should be made as simple as possible, but not simpler.” The word of Einstein is certainly also true for bioengineering.…”

Threading carbon nanotubes through a self-assembled nanotube

“…The functional competence of synthetic materials that mimic nature depends on the precise positioning and synergistic action of multiple, discrete components, which are organized within higher order structures. [1][2][3][4] Composite nanomaterials have shown remarkable potential for applications in biomedicine, 5,6 catalysis 7-11 and energy conversion. [12][13][14] The physical properties of these systems critically rely on the topological and spatial relationships of each domain within the composite.…”