How Enucleated Cytoplasts Are Redefining Cellular Machinery
Exploring the fascinating world of cells without nuclei and their surprising capabilities
Imagine a bustling city, humming with activity. This is a living cell, long described in textbooks as a membrane-bound structure with a commanding nucleus at its center. But what if we could remove city hall and find the metropolis not only still functioning, but in some ways working even more efficiently? This isn't science fiction—it's the fascinating reality of cytoplasts, cellular structures that retain their cytoplasm and membrane but lack a nucleus 3 .
Once a mere biological curiosity, cytoplasts have emerged as powerful tools reshaping our understanding of cellular mechanics, reprogramming, and even the physical forces that animate life itself.
Recent discoveries have overturned fundamental assumptions, revealing that the nucleus is less dense than its surrounding cytoplasm and that enucleated cells maintain remarkable structural integrity and function 2 3 . This article explores how these "empty" cells are teaching us volumes about life's essential processes.
Complete cellular structure with nucleus containing genetic material and cytoplasm with organelles.
Enucleated cell retaining cytoplasm and membrane but lacking genetic material.
For decades, scientists envisioned the nucleus as the cell's densest, most crowded compartment, packed tightly with DNA and proteins. However, a groundbreaking 2025 study published in Nature Communications revealed the opposite: the nucleus is actually less dense than the surrounding cytoplasm across organisms from yeast to human cells 2 .
This discovery, made possible by advanced light-based techniques that measure density at microscopic scales, suggests that fundamental physical principles of pressure balance govern cellular organization in ways we barely understood. The finding has profound implications—when this delicate density balance is disrupted, as in aging or diseased cells, the nucleus becomes denser than the cytoplasm, pointing to density as a crucial indicator of cellular health 2 .
If removing the nucleus doesn't cause cellular collapse, what actually provides a cell's structural integrity? The answer lies in the cytoskeleton—an intricate network of protein filaments that maintains cellular shape and enables movement 1 7 .
Surprisingly, research shows that cytoplasts often retain or even increase stiffness after enucleation. The actomyosin network (a combination of actin filaments and myosin motor proteins) appears to dominate cellular mechanics more than the nucleus itself 3 . This mechanical resilience allows cytoplasts to maintain essential functions, including cellular migration, challenging the long-held view of the nucleus as the cell's primary structural organizer.
| Feature | Whole Cell | Cytoplast |
|---|---|---|
| Nucleus | Present | Absent (enucleated) |
| Genetic Material | DNA in nucleus | None |
| Structural Integrity | Maintained by nucleus and cytoskeleton | Maintained primarily by reinforced cytoskeleton |
| Cellular Functions | Full capabilities, including reproduction | Limited to metabolic processes, transport, migration |
| Primary Applications | Natural cellular processes | Cellular reprogramming, cloning, mechanical studies |
How do researchers probe the physical properties of cells and cytoplasts? A compelling approach was detailed in a reviewed preprint from eLife, where scientists investigated whether the cytoplasm could sustain intracellular pressure gradients 6 .
An atomic force microscope (AFM) cantilever tip was used to indent the cell surface at specific locations, creating a controlled deformation.
Fluorescent beads attached to the cell surface were tracked using defocusing microscopy, which detects nanometer-scale vertical displacements by analyzing changes in diffraction patterns.
Researchers altered cytoplasmic properties by increasing extracellular osmolarity, effectively changing the "pore size" within the cytoplasmic meshwork.
Finite element simulations helped interpret the experimental data and understand the underlying physics.
The experiments revealed that local deformations trigger cell-scale mechanical equilibration lasting several seconds—far longer than previously appreciated 6 . This slow relaxation phase reflects the poroelastic nature of the cytoplasm, behaving like a fluid-filled sponge where shape changes require intracellular fluid redistribution.
When scientists increased osmolarity, reducing cytoplasmic pore size, the equilibration time increased approximately 3.5-fold, confirming that the speed of mechanical response depends on hydraulic permeability 6 . Most remarkably, the research demonstrated that stable pressure gradients can persist for minutes—sufficient to influence processes like cell migration.
| Experimental Condition | Observed Effect | Implication |
|---|---|---|
| Local surface indentation | Biphasic response: fast initial movement followed by slow relaxation | Cytoplasm behaves as a poroelastic material |
| Increased distance from indentation site | Longer relaxation time (τ_p) | Stress equilibration occurs across cellular scales |
| High osmolarity medium | 3.5-fold increase in equilibration time | Cytoplasmic pore size affects hydraulic permeability |
| Sustained deformation | Pressure gradients maintained for minutes | Gradients may drive intracellular flows relevant to migration |
These findings suggest that pressure-driven mechanisms may play a much greater role in cell physiology than currently appreciated, potentially influencing everything from mechanotransduction (how cells convert mechanical signals into biochemical responses) to cellular migration patterns 6 .
Studying cytoplasts and cellular mechanics requires specialized tools and reagents. The following table outlines key materials used in this field, drawing from methodologies described across multiple studies:
| Reagent/Tool | Primary Function | Application Examples |
|---|---|---|
| Optical Stretcher | Measures mechanical properties using light-induced forces | Determining density and stiffness of cellular components 2 |
| Cryo-Electron Tomography | "Freezes" cells in time for high-resolution imaging | Discovering new organelles like hemifusomes 4 |
| Atomic Force Microscope (AFM) | Applies precise forces and measures cellular deformation | Indenting cell surface to study pressure propagation 6 |
| Fluorescent Beads with Defocusing Microscopy | Tracks nanometer-scale cellular movements | Monitoring surface displacement after mechanical stimulation 6 |
| Nuclear Transport Receptors | Serve as molecular "passports" for nuclear entry | Studying nucleocytoplasmic transport through NPCs 5 |
| Dynamin Proteins | Membrane-remodeling molecules essential for fission | Investigating mitochondrial division and cellular processes 8 |
Advanced microscopy techniques enable visualization of cellular structures at unprecedented resolution.
Precision instruments measure cellular forces, stiffness, and mechanical properties.
Specialized reagents and markers enable tracking of specific cellular components and processes.
The comparison between whole cells and cytoplasts reveals a continuum of biological organization:
Whole cells represent nature's complete package, containing both the genetic blueprint (nucleus) and the operational machinery (cytoplasm). The sophisticated communication between these compartments is mediated by nuclear pore complexes (NPCs)—remarkable gatekeepers that allow millions of molecules to pass between nucleus and cytoplasm each minute while maintaining precise selectivity 5 .
Cytoplasts, in contrast, represent specialized cellular machinery that can operate independently of direct genetic control. Their capabilities—from maintaining structural integrity through cytoskeletal networks to facilitating cellular reprogramming—demonstrate that many essential cellular functions are embedded throughout the cell, not solely governed by the nucleus 3 .
This understanding has opened revolutionary applications, particularly in cellular reprogramming and regenerative medicine. Cytoplasts from human embryonic stem cells contain reprogramming factors that can reset somatic cells to a pluripotent state without genetic modification, offering potential pathways for future therapies that avoid the risks of tumor formation associated with other stem cell approaches 3 .
The study of cytoplasts has transformed from a biological curiosity to a field offering profound insights into life's fundamental processes. By isolating cytoplasmic function from nuclear control, scientists have discovered that cellular organization, mechanics, and information processing are distributed properties that cannot be fully understood by studying the nucleus alone.
Recent discoveries—from the unexpected density relationships between nucleus and cytoplasm to the ability of cytoplasts to maintain pressure gradients and structural integrity—highlight how much remains to be learned about cellular function. As research continues to unravel the mysteries of cellular organization, cytoplasts stand as powerful reminders that sometimes, to understand the whole, we must first examine the parts working independently.
This knowledge doesn't diminish the importance of the nucleus but rather places it in context as one component—albeit a crucial one—in the complex, integrated system that is a living cell. The silent partner, it turns out, has been speaking all along—we just needed to learn how to listen.