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Out-of-Equilibrium (Supra)molecular Systems and Materials: An Introduction

Nicolas Giuseppone1 and Andreas Walther2

1University of Strasbourg, Department of Chemistry, Institut Charles Sadron - CNRS, 23 rue du Loess, 67034 Strasbourg, Cedex 2, France

2University of Mainz, Department of Chemistry, Duesbergweg 10-14, 55128 Mainz, Germany

1.1 General Description of the Field

1.1.1 Background, Motivation, and Interdisciplinary Nature of the Topic

What is life? What can we learn from living systems for the design of advanced (supra)molecular systems? What could the new properties of such systems be? Where will such systems find their applications in the future? And once we will have constructed such lifelike systems, will we better understand life itself? These are emerging and stimulating questions at the interface of biology, biological engineering, synthetic biology, origin-of-life research, molecular chemistry, supramolecular self-assembly, systems chemistry, nanoscience, and materials science. This book serves to be a switchboard for connecting conceptual advances in these disciplines to the overarching topic of out-of-equilibrium (supra)molecular systems engineering.

Living systems, first on foremost, inspire with their capability for self-organization leading to the formation of emergent functions such as self-regulation, adaptation, evolution, and self-replication. Examples can be extremely widespread across all scales: (i) development of human societies, (ii) predator/prey (fox/rabbit) oscillators on isolated islands, (iii) swarm behavior of flocks of bird or schools of fish, (iv) quorum sensing in certain bacteria that turn luminescent collectively upon reaching a critical population density, (v) morphogenesis in an embryo, or (vi) cell division. Many of the underlying molecular principles at the small scale have been unraveled by molecular biology in the recent decades. One of the key natural principles for complex and emergent behavior is the ability to make sense of a complex sensory landscape to define a precise output behavior. This is done via biological signaling reaction networks that provide localized computational power using principles such as autocatalytic activation, negative feedback loops, memory modules, timer clocks, and more. The circadian clock setting our day and night rhythm and its adaptation during long-distance travel (jet lag) is a formidable example to highlight how a biological reaction network regulates humans in an oscillating state between asleep and awake and how this reaction network adapts to different time zones by changes in daylight settings (Figure 1.1) [3-5]. Understanding and mimicking such reaction networks to process signal inputs and to provide functional output is one key component for future out-of-equilibrium molecular systems [1, 6, 7]. This complex behavior does however not come for free, and energy needs to be spent to allow for it.

Erwin Schrodinger once said: "Living matter avoids to decay to equilibrium"[8]. This is a striking energetic description of living systems and is in stark contrast to how researchers have been organizing synthetic molecular systems in the past - with a focus toward equilibrium. The aspects of how life organizes matter to not decay to equilibrium heavily depend on the molecular machinery in the body. By often using the energy primarily provided through the hydrolysis of ATP (adenosine triphosphate) and GTP (guanosine triphosphate), living systems are able to perform work on their environment and establish active behavior. This, for instance, refers to the development of concentration gradients by powering ion pumps [9, 10], while other motor proteins are able to transport cargo (kinesin on microtubule tracks) [2, 11-15], lead to muscle contraction (actin/myosin) [11, 16, 17], or provide the flagellar motion propelling bacteria [9, 10, 18, 19] (Figure 1.1). Even when looking at structural proteins in the cytoskeleton, it is important to realize that microtubules and actin filaments are formed in a thermodynamically uphill-driven process consuming chemical energy [2, 20]. It is obvious that in some cases, the energy is just needed to execute a function or distribute resources in a cell, while for other cases the energy is in fact needed to build up a function. By driving a system energetically uphill and storing the energy, a system can react much faster. This is, for instance, seen in the ion gradients at our nerve cells, where the buildup of the action potential allows for very fast signal propagation by simple signal-induced opening of an ion channel - much faster than the comparably slow active ion pump transporter protein could provide a signal [9, 10]. Being in such a metastable energy-rich state is helpful for fast reactivity ("spun like a spring"). Similarly, driving self-assembling systems, such as the microtubules in our cytoskeleton, out of equilibrium, by coupling their structure formation processes to the dissipation of chemical fuels, allows to reach very unusual dynamics in the form of dynamic instabilities [21]. These dynamic instabilities with concurrent polymerization and depolymerization of the microtubule filaments, and recycling of the building blocks, enable the cytoskeleton to be in a flux-like, highly adaptive, dynamic steady state so that its structure can be quickly reconfigured to new sensory input. Even though it feels like a waste of energy to run such structures uphill in an energy-consuming way, the much faster capacity for adaptive reconfiguration is a key functional benefit [22, 23]. Understanding and controlling energy management and understanding how to reach controlled energy-driven nonequilibrium states are a second key aspect for the design of future out-of-equilibrium molecular systems.

Tremendous progress has been made in the recent decades in synthetic (supra)molecular systems and materials, molecular machines and motors, self-assembly research, synthetic biology and chemical reaction network, as well as soft matter and bionanoscience, and materials research. Although a completely exhaustive picture is not the focus of this introduction, we wish to point to a few main developments that will also set the basis for the individual chapters of this book.

Figure 1.1 Selected out-of-equilibrium systems in living nature. 1. Biological regulatory networks for autonomous temporal control. (A) Schematic representation of the downregulation of "a" production by "b," symbolized by an arrow with a flat head (top), and an exemplarily corresponding reaction profile, where the amount of signal "b" is positively correlated with the activation barrier of formation of "a" (bottom). (B) Schematic representation and reaction rate profile of a delayed negative feedback, where the delay induced by the transformation of "a" into "b" is represented by an arrow with empty head. (C) Autocatalytic positive feedback for the formation of "a," symbolized by an arrow with a filled head (top), and the corresponding reaction profile, where "a" decreases its own activation barrier of formation (bottom). (D) Schematic representation of the hierarchical circadian network, in which the core clock synchronizes the metabolic clock in the lungs while being regulated by the day/night cycles. (E) Real-time visualization of PER2 gene (PER) expression using PER::luciferase fusion proteins in the suprachiasmatic nucleus (core oscillators) and in lungs (peripheral oscillators) in mice. Tissues were explanted at day 0.5; white and dark lines show day/night cycles. (F) Schematic representation of the feedback loops controlling circadian oscillations. 2. Out-of-equilibrium dissipative structures for microtubule self-assembly and dynamics. (G) Schematic representation of dynamic instabilities during microtubule polymerization. (H) Immunofluorescence images showing DNA (in blue) and microtubules (in green) during human cell division. Energy-driven molecular machines and motors: schematic representation of (I) the coordinated walk of kinesin motors on microtubules fueled by ATP hydrolysis and (J) the ATP-powered flagellar propulsion of bacteria.

Source: (a-d, i, j) Merindol and Walther 2017 [1]. © 2017, Royal Society of Chemistry, (f-h) Cheeseman and Desai [2]. © Springer nature, (e) Yoo et al. [3]. (H) Reproduced from Merindol and Walther with permission from The Royal Society of Chemistry.

The wide field of self-assembly with components from organic supramolecular chemistry, from polymer and colloid science, and from the biological domain has matured largely [24-34]. Researchers worldwide are able to design hierarchical and highly complex architectures from the bottom-up with an exquisite control over interactions and organization. However, all of these structures are typically designed by self-assembly and self-sorting toward thermodynamic equilibrium. This progress in experimental systems has been greatly assisted by developments in computer simulations that are able to predict and rationalize structural space using concepts of energy minimization. Such structures have become switchable by the integration of molecular switches, responsive macromolecules, or tunable colloidal interactions. Concurrently, this has given rise to the field of responsive materials...