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Nanobiomechanics (also bionanomechanics) is an emerging field in nanoscience and biomechanics that combines the powerful tools of
nanomechanics Nanomechanics is a branch of ''nanoscience'' studying fundamental ''mechanical'' (elastic, thermal and kinetic) properties of physical systems at the nanometer scale. Nanomechanics has emerged on the crossroads of biophysics, classical mechanics, s ...
to explore fundamental science of biomaterials and biomechanics. Since the introduction by its founder Yuan-Cheng Fung, the field of biomechanics has become one of the branches of mechanics and bioscience. For many years, biomechanics has examined tissue. Through advancements in nanoscience, the scale of the
force In physics, a force is an influence that can change the motion of an object. A force can cause an object with mass to change its velocity (e.g. moving from a state of rest), i.e., to accelerate. Force can also be described intuitively as a p ...
s that could be measured and also the scale of observation of biomaterials was reduced to "nano" and "pico" level. Consequently, it became possible to measure the mechanical properties of biological materials at nanoscale. This is relevant to improve tissue engineering processes and cellular therapy. Most of the biological materials have different hierarchical levels, and the smallest ones refer to the nanoscale. For example,
bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
has up to seven levels of biological organization, and the smallest level, i.e., single
collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
fibril Fibrils (from the Latin ''fibra'') are structural biological materials found in nearly all living organisms. Not to be confused with fibers or filaments, fibrils tend to have diameters ranging from 10-100 nanometers (whereas fibers are micro ...
and hydroxylapatite minerals have dimensions well below 100 nm. Therefore, being able to probe properties at this small scales provides a great opportunity for better understanding the fundamental properties of these materials. For example, measurements have shown that nanomechanical heterogeneity exists even within single collagen fibrils as small as 100 nm. One of the other most relevant topics in this field is measurement of tiny forces on living cells to recognize changes caused by different
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
s, including disease progression. For example, it has been shown that
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s infected by
malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
are 10 times stiffer than normal cells. Likewise, it has been shown that cancer cells are 70 percent softer than normal cells. Early signs of aging
cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...
and
osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...
has been shown by looking at the changes in the tissue at the nanoscale.


Methods, instrumentation, and application

The common methods in nanobiomechanics include
atomic force microscopy Atomic force microscopy (AFM) or scanning force microscopy (SFM) is a very-high-resolution type of scanning probe microscopy (SPM), with demonstrated resolution on the order of fractions of a nanometer, more than 1000 times better than the op ...
(AFM), nanoindentation, and application of
nanoparticles A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 1 ...
. These and other methods may be applied to relevant materials, for example: bone and its hierarchical constituents such as single collagen fibrils, single living cells,
actin filaments Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other pr ...
and
microtubules Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27  nm and have an inner diameter between 11 an ...
.


Atomic Force Microscopy

For a description of atomic force microscopy (AFM), see
atomic force microscopy Atomic force microscopy (AFM) or scanning force microscopy (SFM) is a very-high-resolution type of scanning probe microscopy (SPM), with demonstrated resolution on the order of fractions of a nanometer, more than 1000 times better than the op ...
. AFM has been used to study the nanoscale level of the
cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
and its components, the
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
, and the cell's environment. Understanding the cell's mechanics, including at a nanoscale level, is highly connected to understanding these molecules and structures. As all of this affects how the cell behaves, it is beneficial for tissue engineering. One example of this is when researchers applied tapping mode AFM to study repair bone from genetically modified mesenchymal cells. Via this method, they were able to image structures in the bone on a nano scale that suggested collagen was present. AFM has also been applied to measure the mechanical properties of
proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
and other biomolecules in a variety of conditions through extension and compression experiments. Further, it has been applied to the mapping of cells' and membranes' mechanical properties, mechanotransduction, how cells adhere or detach based on the surface they are on and their own molecules, and the stiffness of cells. As metastatic cells have been shown to be softer than benign cells using AFM, the mechanics of cancer cells may be useful to diagnose cancer.


Nanoindentation

For a description of nanoindentation, see nanoindentation. Nanoindentation has been applied to biomechanical studies. One example studied repair bone from genetically modified mesenchymal cells. They compressed a probe with a nanometer radius into both native and repair bone and used it to study the deformability of the tissue. This gave them insight into mechanical properties of the bone, including its stiffness. Nanoindentation also allowed them to study the bone’s compressibility through loading and unloading curves. Further, nanoindentation may be combined with other methods in specific studies. One example is AFM nanoindentation, which has been applied to study subcellular components in living
cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
.


Nanoparticles

For a description of nanoparticles, see
nanoparticles A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 1 ...
. Nanoparticles both affect cells on a nanoscale level, and are one method of studying the mechanical properties of cells and biomaterials on the nanoscale level. Nanoparticles affect how cells adhere to substrates, and the cell’s stiffness. They also impact components of the cell’s
cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
which in turn affect
cell motility Motility is the ability of an organism to move independently, using metabolic energy. Definitions Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...
as they bind and interact with structures such as receptors and
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
. As these nanoparticles affect the nanobiomechanics of
cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
, they are valuable tools to study them. For example, nanoparticles have been embedded on the surfaces of structures to alter the nanotopographical environment, and affected how the cell behaved. This included how cells spread, how cytoskeletal components assemble, and how cells attach. Some included nanoparticles have
magnetic properties Magnetism is the class of physical attributes that are mediated by a magnetic field, which refers to the capacity to induce attractive and repulsive phenomena in other entities. Electric currents and the magnetic moments of elementary particles ...
, and have been used in conjunction with magnetic fields for detailed control of cellular surfaces and other studies. Nanoparticles are useful in studying the ways cells adapt physical forces into biochemical signals, and the mechanical properties of cellular constituents. They have also been used in processes such as particle tracking microrheology.


Computational nanobiomechanics

In addition to experimental aspect, research has been expanding through computational methods. Molecular dynamics (MD) simulations have provided a wealth of knowledge in this area. Although, the MD simulation are still limited to a small number of atoms and molecules, due to limitation in the computational performance, they have proved to be an instrumental branch of this emerging field.


References

{{Reflist Nanotechnology Biomechanics