The capability to sense and respond to external mechanical stimuli at various timescales is essential to many physiological aspects in plants, including selfprotection, intake of nutrients and reproduction. Remarkably, some plants have evolved the ability to react to mechanical stimuli within a few seconds despite a lack of muscles and nerves. The fast movements of plants in response to mechanical stimuli have long captured the curiosity of scientists and engineers, but the mechanisms behind these rapid thigmonastic movements are still not understood completely. In this article, we provide an overview of such thigmonastic movements in several representative plants, including Dionaea, Utricularia, Aldrovanda, Drosera and Mimosa. In addition, we review a series of studies that present biomimetic structures inspired by fast-moving plants. We hope that this article will shed light on the current status of research on the fast movements of plants and bioinspired structures and also promote interdisciplinary studies on both the fundamental mechanisms of plants' fast movements and biomimetic structures for engineering applications, such as artificial muscles, multi-stable structures and bioinspired robots.

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Exogenous mechanical forces are transmitted through the cell and to the nucleus, initiating mechanotransductive signaling cascades with profound effects on cellular function and stem cell fate. A growing body of evidence has shown that the force sensing and force-responsive elements of the nucleus adapt to these mechanotransductive events, tuning their response to future mechanical input. The mechanisms underlying this “mechano-adaptation” are only just beginning to be elucidated, and it remains poorly understood how these components act and adapt in tandem to drive stem cell differentiation. Here, we review the evidence on how the stem cell nucleus responds and adapts to physical forces, and provide a perspective on how this mechano-adaptation may function to drive and enforce stem cell differentiation.

cues, or "mechanical memory," results from the stable remodeling of various components of the cell. Defining of the mechanisms by which the cell forms and maintains mechanical memories will forward the development of new biomaterials with improved cell functionality. Importantly, converging strands of evidence have implicated the cell nucleus, the storehouse of the genome, as a critically important adaptive mechanosensor in all cells. [2,3] In particular, recent evidence has shown that forces can be directly transmitted to chromatin to alter gene expression. [4] In this review, we discuss the central importance of the cell nucleus and chromatin in understanding and manipulating mechanobiological pathways, and the manner in which extracellular mechanical cues are "looped in" (that is, transmitted to, interpreted by, and stored in) the epigenome and chromatin organization to direct cell fate. In Section 2, we define a framework for understanding how cells sense, transduce, and remember mechanical cues. In Section 3, we provide an overview of how the cell nucleus senses, transduces and adapts to mechanical forces. Following this, we describe in Section 4 how mechanical memories might be encoded within organized chromatin through molecular signaling as well as direct force-induced structural rearrangements. Finally, we conclude in Section 5, outlining new directions for the field in reducing this new knowledge to practice. Mechanotransduction and Mechanical MemoryIn this section, we review the concepts of mechanotransduction and mechanical memory in the mammalian cell. MechanotransductionThe last decade has witnessed a number of technological advances that enable the study of cell mechanics down to the sub-protein level, fostering a new understanding of the role of mechanobiological mechanisms in governing cell behavior (for a comprehensive overview of this topic, please refer to the following reviews [5,6] ). Indeed, it is now well accepted that mechanical cues play a fundamental role in directing cell behavior. Cells sense exogenous mechanical forces in addition to exerting their own. These processes are accomplished through the mechanobiological machinery of the cell-the force sensing (e.g., integrin based focal adhesions), [7] transmitting Cells respond to physical cues in their microenvironment. These cues result in changes in cell behavior, some of which are transient, and others of which are permanent. Understanding and leveraging permanent alteration of cell behavior induced by mechanical cues, or "mechanical memories," is an important aim in cell and tissue engineering. Herein, this paper reviews the existing literature outlining how cells may store memories of biophysical cues with a specific focus on the nucleus, the storehouse of information in eukaryotic cells. In particular, this review details mechanically driven adaptations in nuclear structure and genome organization and outlines potential mechanisms by which mechanical memories may be encoded within the structure and organization of the nucleus and ...

During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left-right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination of experiments, a physical model of the embryonic morphology and mechanics analysis that the vitelline membrane (VM) exerts an external load on the brain that drives torsion. Our theoretical analysis showed that the force is of the order of 10 micronewtons. We also designed an experiment to use fluid surface tension to replace the mechanical role of the VM, and the estimated magnitude of the force owing to surface tension was shown to be consistent with the above theoretical analysis. We further discovered that the asymmetry of the looping heart determines the chirality of the twisted brain via physical mechanisms, demonstrating the mechanical transfer of left-right asymmetry between organs. Our experiments also implied that brain flexure is a necessary condition for torsion. Our work clarifies the mechanical origin of torsion and the development of left-right asymmetry in the early embryonic brain.

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Cadherin-17 (CDH17) is an adhesion molecule that binds to self and integrin a2b1, its expression in the adult is limited to gastrointestinal tissue and is involved in cancer progression. CDH17 is expressed de novo or overexpressed in several gastro-intestinal cancers including colorectal, gastric and pancreatic, making it an ideal target for immunotherapies. A humanized bifunctional antibody was developed, ARB-201, that binds to both CDH17 and the CD3/TCR complex (CD3) with high affinity. ARB-201 induced retargeted T cell cytotoxicity was determined in a 2D and 3D model. Relative to 2D, cytotoxicity of 3D tumors may be considered more predictive of efficacy for solid tumors. DLD-1, a colorectal adenocarcinoma cell line, was targeted in the 2D and 3D T cell cytotoxicity assays. Pre-labeled DLD-1 were grown in standard 384-well microplate (2D) or Kuraray's 384-well Elplasia microplates (3D). Effector PBMCs, freshly isolated from healthy donors were added to the target DLD-1 cells containing a concentration response curve of ARB-201. Samples were evaluated for the specific cellular cytotoxicity using cell imaging. The results show at 48 hours an EC50 of 12 pM for 2D and 47 pM for the 3D model. ARB-201 induced potent T cell cytotoxicity of DLD-1. Although cytotoxicity in the 3D tumor model was relatively less, we observed an increase over time, demonstrating that ARB-201 progressively kills 3D tumor cells and possesses cytotoxic activity that may translate into clinical efficacy for solid tumors. Citation Format: Macarena Irigoyen, Eric Dai, John Luk, Gonzalo Castillo, Don Staunton. Evaluation of retargeted T cell cytotoxicity of a bispecific antibody targeting CDH17 and CD3 in 2D- and 3D-colon cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5608.