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Cells rely on their cytoskeleton for key processes including division and directed motility. Actin filaments are a primary constituent of the cytoskeleton. Although actin filaments can create a variety of network architectures linked to distinct cell functions, the microscale molecular interactions that give rise to these macroscale structures are not well understood. In this work, we investigate the microscale mechanisms that produce different branched actin network structures using an iterative classification approach. First, we employ a simple yet comprehensive agent-based model that produces synthetic actin networks with precise control over the microscale dynamics. Then we apply machine learning techniques to classify actin networks based on measurable network density and geometry, identifying key mechanistic processes that lead to particular branched actin network architectures. Extensive computational experiments reveal that the most accurate method uses a combination of supervised learning based on network density and unsupervised learning based on network symmetry. This framework can potentially serve as a powerful tool to discover the molecular interactions that produce the wide variety of actin network configurations associated with normal development as well as pathological conditions such as cancer. 

Virtually all forms of life, from single-cell eukaryotes to complex, highly differentiated multicellular organisms, exhibit a property referred to as symmetry. However, precise measures of symmetry are often difficult to formulate and apply in a meaningful way to biological systems, where symmetries and asymmetries can be dynamic and transient, or be visually apparent but not reliably quantifiable using standard measures from mathematics and physics. Here, we present and illustrate a novel measure that draws on concepts from information theory to quantify the degree of symmetry, enabling the identification of approximate symmetries that may be present in a pattern or a biological image. We apply the measure to rotation, reflection and translation symmetries in patterns produced by a Turing model, as well as natural objects (algae, flowers and leaves). This method of symmetry quantification is unbiased and rigorous, and requires minimal manual processing compared to alternative measures. The proposed method is therefore a useful tool for comparison and identification of symmetries in biological systems, with potential future applications to symmetries that arise during development, as observed in vivo or as produced by mathematical models. This article is part of the theme issue ‘Recent progress and open frontiers in Turing’s theory of morphogenesis’. 

Abstract In developmental biology as well as in other biological systems, emerging structure and organization can be captured using time-series data of protein locations. In analyzing this time-dependent data, it is a common challenge not only to determine whether topological features emerge, but also to identify the timing of their formation. For instance, in most cells, actin filaments interact with myosin motor proteins and organize into polymer networks and higher-order structures. Ring channels are examples of such structures that maintain constant diameters over time and play key roles in processes such as cell division, development, and wound healing. Given the limitations in studying interactions of actin with myosin in vivo, we generate time-series data of protein polymer interactions in cells using complex agent-based models. Since the data has a filamentous structure, we propose sampling along the actin filaments and analyzing the topological structure of the resulting point cloud at each time. Building on existing tools from persistent homology, we develop a topological data analysis (TDA) method that assesses effective ring generation in this dynamic data. This method connects topological features through time in a path that corresponds to emergence of organization in the data. In this work, we also propose methods for assessing whether the topological features of interest are significant and thus whether they contribute to the formation of an emerging hole (ring channel) in the simulated protein interactions. In particular, we use the MEDYAN simulation platform to show that this technique can distinguish between the actin cytoskeleton organization resulting from distinct motor protein binding parameters.