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From Mechanochemistry to Mechanoresponsive Materials

Lasith S. Kariyawasam, Connor Filbin, Cameron Locke, and Ying Yang

University of Nevada, Department of Chemistry, Virginia Street, Reno, NV, 89557, USA

1.1 Introduction

Our skin can sense the touch by a series of mechanotransduction mechanisms. Kneading bread dough uncoils gluten proteins, creating an elastic macromolecular network that gives the dough toughness. Stretching or scratching a piece of plastic is likely to break covalent bonds. These processes involve reactions that are activated by mechanical energy, which are prevalent in our daily lives. However, they are less commonly discussed compared to thermochemical, photochemical, or electrochemical reactions. Mechanoactivated reactions have been reported dating back to 315 BCE. These early accounts describe grinding native cinnabar in a copper mortar with a copper pestle in the presence of vinegar to yield the reduction product, mercury. However, it was not until the nineteenth century that systematic studies were conducted [1]. In 1860s, Carey Lea showed that grinding mercury and silver halides in a pestle and mortar at room temperature favors decomposition, whereas heating only leads to melting or sublimation without any decomposition [2]. This discovery provided clear evidence that mechanochemical reactions are distinctively different from thermal ones. Mechanochemistry was, therefore, classified as the fourth type of chemical reaction by Ostwald in 1919 [3].

The first widely accepted definition for mechanochemistry was formulated by Heinicke in 1984 [1], that mechanochemistry is a branch of chemistry, which is concerned with chemical and physicochemical transformations of substances in all states of aggregation produced by the effect of mechanical energy. IUPAC defines it as the chemical reaction that is induced by the direct absorption of mechanical energy [4]. In fact, the definition is still under extensive debate. Molecular motors, which convert chemical energy into mechanical work, certainly do not fit into these definitions. However, the motions generated by molecular motors can apply force to the surrounding molecules to induce a cascade of subsequent reactions. Such topic is of great interest to chemists and engineers working in the field of mechanochemistry. The lack of unification and slow progress since the establishment of mechanochemistry in the nineteenth century reflects the complexity and the lack of understanding of the scope and mechanisms for such reactions. Recently, mechanochemical research has intensified through the use of new tools developed for mechanistic studies and the opportunities to create functional materials [5-12]. As mechanochemical reactions occur for both small and macromolecules, ongoing research can be clarified in four sub-areas: developing novel and scalable mechanochemical synthesis to make useful chemicals via environmental-friendly solvent-free processes; understanding biomechanochemistry, such as motor proteins, mechanosensing, and mechanotransduction mechanisms; creating mechanoresponsive polymeric materials for which mechanical forces become constructive for technological advances; and investigating the molecular mechanisms through simulations and single-molecular force experiments.

In this chapter, we will focus on the fundamental aspects of polymer mechanochemistry that are the key elements in designing mechanoresponsive materials. We will start with a brief introduction of the role of mechanochemistry in biological systems as a springboard for inspiration. The mechanistic aspects of mechanochemistry in general terms, from small molecules to polymer mechanochemistry, will then be discussed to show the unique bond-activation mechanisms. The force-responsive molecules, named mechanophores, can depend on the cleavage of either covalent or noncovalent bonds. The activation energy, dynamics, and reversibility can be tuned via various structural properties. Therefore, the chemistry of these two classes of mechanophores will be covered in detail. There are different mechanical sources for generating mechanical energy, such as shearing, stretching, grinding, ball milling, and sonication. These methods differ in the direction of force, frequency, and heat formation, leading to different effects on molecular distortion and kinetics. However, this chapter will focus on the chemistry of mechanoresponsive bonds within polymer materials regardless of the type of applied force.

1.2 Mechanochemistry in Biological Systems

A powerful source of inspiration for improving the design of polymer materials is Nature as mechanochemical systems are ubiquitous in organisms. A wealth of knowledge can be gained because biological systems have evolved elegant mechanoresponsive arrangements that are critical for supporting and maintaining life. They often involve complicated processes via coherently organized biopolymer networks. A cell, for example, is constantly under mechanical stress, including tension, osmosis, compression, and shear forces. Upon mechanical deformation, feedback from proteins in the cell cytoskeleton activates a variety of mechanosensors that work in unison to create a response in the cell nucleus via multiple mechanotransduction events [13]. As shown in Figure 1.1, the mechanism begins by transducing force through the cell membrane to microfilaments and microtubules of the cytoskeleton in the cytoplasm. Subsequently, cytoskeletal changes directly affect nucleoskeletal proteins called lamina. This has an explicit effect on the spatial arrangement of lamin-bound intermediate filaments as well as chromosomes, as they are anchored to nuclear lamina [14]. Shifts in chromosome packing affect gene expression, which allows key biological functions in response to force, such as survival, motility, reproduction, and differentiation. These events in cells play important roles in maintaining homeostasis and preventing disease in the body. Although understanding of many of these biological pathways is still limited, we will discuss a few chemistries known to be involved in these processes as inspirations for material design.

Figure 1.1 Intra- and extracellular forces stimulate a cell in an interconnected system of reactions causing complete change of structure and resulting cell function. Source: Adapted with permission from Tsimbouri [13]. Copyright 2015 MDPI.

1.2.1 A Stressful Environment During Heart Development

In a vertebrate embryo, the heart first starts as a tube composed of primarily early cardiomyocytes, the cardiac muscle cells that drive the heart contraction. It quickly differentiates into different parts and morphologies. As the embryo grows, the contractile capacity of the cardiomyocytes increases to provide greater driving forces to pump more blood. Meanwhile, the extracellular matrix (ECM) surrounding the cardiomyocytes must increase in its stiffness parallelly to keep a proper tissue mechanical integrity with the increasing contractile stress. Cells in connective tissue, called fibroblasts, secrete collagen and other matrix proteins to maintain the structural framework. Therefore, during the development of the heart, a balance between cardiac fibroblast and cardiomyocyte cell populations must be established to maintain muscle contraction along with a significant collagenous matrix. There is mounting evidence suggesting that mechanical stress itself plays important role in directing tissue growth with mechanochemical feedback loops for gene and protein expression [15]. In comparison, the brain tissue in a low-stress environment does not show the same development in stiffness, although a recent study found strong mechanical interactions of the synapses [16] which may be a critical mechanism in brain functions, indicating the broad involvements of mechanochemistry and mechanotransduction in numerous bioprocesses.

During embryonic heart development, many mechanosensitive pathways have been linked to the proper functions of the myocyte and fibroblast cells. Majkut et al. surveyed literature evidence and proposed the network model for understanding how contraction against tissue stiffness affords a functional equilibrium between the cell types [15]. On one hand, cardiomyocytes produce contractile stress that promotes the expression of matrix structural proteins by fibroblasts. On the other hand, as contraction must effectively strain the heart tissue, it is postulated that the proliferation of fibroblasts is limited by the stiffness of their environment and thus collagenous matrix density. Additionally, the model suggests that stabilizing matrix collagen and degradation of motor proteins under strained conditions are also important in regulating tissue stiffness. The stabilization may be related to inhibited protease binding to collagen fibers or kinase binding to myosin minifilaments when they are under tension, thus preventing their dissociation and digestion. A model of dynamic cell-matrix interaction is also extended to nuclear mechanics because during development there are variations in lamin levels that appear to correlate with ECM mechanics [15]. As previously discussed, mechanical signals from the extracellular environment can be physically transmitted by the contractile cytoskeleton to the nucleus by connections through the nuclear membrane to the nuclear lamina. Lamina can interact with chromatin and various proteins that regulate transcription. Therefore, lamin...