Will The Cell Elongate During Mitosis

Cell division, a fundamental process of life, involves intricate mechanisms ensuring accurate chromosome segregation and equal distribution of cellular components into daughter cells. Mitosis, the phase of cell division where the nucleus divides, is often associated with cell rounding. However, the question of whether a cell elongates during mitosis is more nuanced and depends on several factors including cell type, experimental conditions, and the specific stage of mitosis.

Introduction

Mitosis is traditionally divided into several distinct phases: prophase, prometaphase, metaphase, anaphase, and telophase. Each phase involves specific structural changes within the cell to facilitate chromosome segregation. While cell rounding is commonly observed, elongation can occur under certain circumstances. This article explores the conditions and mechanisms under which cells might elongate during mitosis, providing a comprehensive overview of this less discussed aspect of cell division.

Cell Rounding During Mitosis: The Conventional View

Why Cells Round Up

During mitosis, cells typically undergo a dramatic change in shape, transitioning from a flattened or elongated interphase morphology to a rounded one. This rounding is attributed to several factors:

• Actomyosin Contractility: Increased activity of the actomyosin cytoskeleton generates contractile forces that pull the cell cortex inwards, leading to a spherical shape. Myosin II, a motor protein, interacts with actin filaments to produce this contraction.
• Detachment from Substrate: Many adherent cells detach from the extracellular matrix (ECM) during mitosis. This detachment reduces the constraints on cell shape imposed by the substrate, allowing the cell to adopt a more spherical configuration driven by cortical tension.
• Changes in Cell Adhesion: Mitotic cells often downregulate cell-cell and cell-matrix adhesion molecules, reducing the adhesive forces that maintain cell shape.

The Molecular Mechanisms of Cell Rounding

The RhoA signaling pathway plays a central role in regulating actomyosin contractility during mitosis. Activation of RhoA leads to the activation of Rho-associated kinase (ROCK), which phosphorylates myosin light chain (MLC), enhancing myosin II activity and contractility. This pathway is tightly regulated to ensure proper cell rounding and division.

Evidence of Cell Elongation During Mitosis

While cell rounding is the widely accepted norm, several studies have reported cell elongation during mitosis, particularly in specific cell types and under certain conditions.

Cell Types Exhibiting Elongation

• Epithelial Cells: In some epithelial tissues, cells maintain a degree of elongation even during mitosis. This is often due to the strong cell-cell adhesion and the structural constraints imposed by the surrounding tissue.
• Fibroblasts: Fibroblasts, which are responsible for producing the extracellular matrix, can exhibit elongation during mitosis, especially when cultured on aligned fibers or within a three-dimensional matrix.
• Neurons: Neuronal cells, with their highly elongated processes, may maintain some of their elongated shape during mitosis, particularly in the developing nervous system.

Conditions Favoring Cell Elongation

• Confinement: When cells are confined within narrow spaces or channels, they may elongate during mitosis due to the physical constraints of the environment.
• Extracellular Matrix (ECM) Interactions: Strong adhesion to an aligned ECM can prevent cell rounding and promote elongation during mitosis.
• Mechanical Cues: Mechanical stimuli, such as tensile forces, can influence cell shape and promote elongation during mitosis.

Mechanisms Underlying Cell Elongation During Mitosis

Role of the Cytoskeleton

The cytoskeleton, composed of actin filaments, microtubules, and intermediate filaments, plays a crucial role in determining cell shape and mechanical properties.

• Actin Filaments: While actomyosin contractility typically promotes cell rounding, specific arrangements of actin filaments can support cell elongation. For example, aligned actin stress fibers can resist cortical tension and maintain an elongated shape.
• Microtubules: Microtubules are essential for spindle formation and chromosome segregation during mitosis. They also contribute to cell shape by exerting pushing forces on the cell cortex. In some cases, microtubules can stabilize elongated cell shapes by interacting with cortical proteins.
• Intermediate Filaments: Intermediate filaments provide structural support and mechanical resilience to cells. In epithelial cells, keratin filaments can maintain cell shape and resist rounding during mitosis.

Influence of Cell-ECM Adhesions

Cell-ECM adhesions, mediated by integrins, anchor cells to the extracellular matrix and transmit mechanical forces.

• Focal Adhesions: Focal adhesions are large protein complexes that link the actin cytoskeleton to the ECM. Strong adhesion to an aligned ECM can prevent cell rounding and promote elongation during mitosis.
• ECM Rigidity: Cells cultured on rigid substrates tend to exhibit increased contractility and rounding during mitosis. Conversely, cells on softer substrates may maintain a more elongated shape.

The Impact of Cell-Cell Adhesions

Cell-cell adhesions, mediated by cadherins and other adhesion molecules, play a crucial role in maintaining tissue integrity and cell shape.

• Cadherins: Cadherins form strong adhesive junctions between cells, providing mechanical support and resisting cell rounding. In epithelial tissues, cadherin-mediated adhesion can maintain cell elongation during mitosis.
• Tight Junctions and Adherens Junctions: These junctional complexes contribute to the overall mechanical stability of epithelial tissues, preventing cell rounding and promoting elongation during mitosis.

Experimental Evidence and Studies

Studies on Epithelial Cells

Several studies have examined cell shape changes during mitosis in epithelial tissues. For instance, research on Madin-Darby Canine Kidney (MDCK) cells has shown that these cells maintain a degree of elongation during mitosis due to strong cell-cell adhesion and the constraints imposed by the surrounding tissue. Time-lapse microscopy and quantitative image analysis have revealed that MDCK cells undergo less rounding compared to isolated cells.

Research on Fibroblasts

Fibroblasts cultured on aligned collagen fibers exhibit elongation during mitosis. These cells maintain their elongated shape due to the strong adhesion to the aligned ECM and the mechanical guidance provided by the fibers. Studies using traction force microscopy have shown that fibroblasts exert significant forces on the ECM during mitosis, which contributes to maintaining their elongated shape.

Investigations on Neuronal Cells

In the developing nervous system, neuronal cells with elongated processes may maintain some of their elongated shape during mitosis. Research on neural progenitor cells has shown that these cells can divide while maintaining connections to the surrounding tissue, which may contribute to maintaining their elongated shape.

Biophysical Considerations

Cortical Tension

Cortical tension, generated by actomyosin contractility, is a key determinant of cell shape during mitosis. High cortical tension promotes cell rounding, while low cortical tension may allow cells to maintain an elongated shape. The balance between cortical tension and other forces, such as cell-ECM adhesion and cell-cell adhesion, determines the overall cell shape.

Mechanical Constraints

Mechanical constraints, such as confinement and ECM rigidity, can influence cell shape during mitosis. Cells confined within narrow spaces or channels may elongate due to the physical limitations of the environment. Similarly, cells on rigid substrates tend to round up, while cells on softer substrates may maintain a more elongated shape.

Force Transmission

Force transmission through the cytoskeleton and cell-ECM adhesions plays a crucial role in determining cell shape during mitosis. Cells exert forces on the ECM and receive mechanical cues from the environment, which can influence their shape and behavior.

The Role of Signaling Pathways

RhoA Signaling

As mentioned earlier, the RhoA signaling pathway is a key regulator of actomyosin contractility. Activation of RhoA promotes cell rounding, while inhibition of RhoA may allow cells to maintain an elongated shape.

Other Signaling Pathways

Other signaling pathways, such as the PI3K/Akt pathway and the MAPK pathway, can also influence cell shape and behavior during mitosis. These pathways regulate cell adhesion, cytoskeletal dynamics, and cell cycle progression, all of which can impact cell shape.

Implications for Tissue Development and Disease

Tissue Morphogenesis

Cell shape changes during mitosis play a critical role in tissue morphogenesis, the process by which tissues and organs are formed during development. The ability of cells to elongate or round up during mitosis can influence tissue architecture and function.

Cancer

Aberrant cell shape changes during mitosis can contribute to cancer development and progression. Cancer cells often exhibit altered cytoskeletal dynamics, cell adhesion, and signaling pathways, which can lead to abnormal cell shapes and behaviors. Understanding the mechanisms that regulate cell shape during mitosis may provide insights into cancer biology and potential therapeutic targets.

Techniques for Studying Cell Shape During Mitosis

Microscopy

Microscopy techniques, such as phase contrast microscopy, fluorescence microscopy, and confocal microscopy, are essential tools for studying cell shape changes during mitosis. Time-lapse microscopy allows researchers to track cell shape changes over time, providing valuable insights into the dynamics of cell division.

Quantitative Image Analysis

Quantitative image analysis techniques, such as cell segmentation, shape analysis, and fluorescence intensity measurements, can be used to quantify cell shape changes during mitosis. These techniques provide objective and reproducible data that can be used to compare cell shapes under different conditions.

Traction Force Microscopy

Traction force microscopy (TFM) is a technique used to measure the forces that cells exert on the ECM. TFM can provide insights into the mechanical interactions between cells and their environment, which can influence cell shape during mitosis.

Atomic Force Microscopy

Atomic force microscopy (AFM) is a technique used to measure the mechanical properties of cells and tissues. AFM can provide information about cell stiffness, elasticity, and adhesion, which can influence cell shape during mitosis.

Future Directions and Open Questions

Exploring the Role of 3D Culture Systems

Three-dimensional (3D) culture systems provide a more physiologically relevant environment for studying cell shape changes during mitosis. These systems allow cells to interact with each other and the ECM in a more natural way, which can influence their shape and behavior.

Investigating the Influence of Mechanical Forces

Mechanical forces play a critical role in regulating cell shape during mitosis. Future research should focus on elucidating the mechanisms by which cells sense and respond to mechanical cues, and how these cues influence cell shape changes.

Elucidating the Molecular Mechanisms

A deeper understanding of the molecular mechanisms that regulate cell shape during mitosis is needed. This includes identifying the key signaling pathways, cytoskeletal proteins, and adhesion molecules that control cell shape changes.

Conclusion

In summary, while cell rounding is the commonly observed phenomenon during mitosis, cell elongation can occur under specific conditions. Factors such as cell type, confinement, ECM interactions, and mechanical cues can influence cell shape during mitosis. The cytoskeleton, cell-ECM adhesions, and cell-cell adhesions play critical roles in determining whether a cell elongates or rounds up during mitosis. Understanding the mechanisms that regulate cell shape during mitosis is crucial for understanding tissue development, disease progression, and for developing new therapeutic strategies. Future research should focus on exploring the role of 3D culture systems, investigating the influence of mechanical forces, and elucidating the molecular mechanisms that govern cell shape changes during mitosis.