Little Miss Muffet

BY MOTHER GOOSE

Little Miss Muffet

Sat on a tuffet,

Eating her curds and whey;

Along came a spider,

Who sat down beside her,

And frightened Miss Muffet away.

Spider silk is a wonder material that, weight for weight, is stronger than steel, tougher than Kevlar and can be more elastic than rubber. It’s also flexible and antimicrobial. Scientists have used silk to make bulletproof armor, violin strings, medical bandages, optical fiber cables and even extravagant clothing.[i]

Spider silk is made of a blend of different proteins linked together into a chain, produced by special glands call spinnerets on the spider’s rear end. All spiders produce silk (some spiders can produce several different kinds), but not necessarily as webs like those depicted in Halloween decorations.

In 1883, the Krakatoa volcano in present-day Indonesia erupted with the force of over 10,000 hydrogen bombs, obliterating most of the island and converting it into a lifeless wasteland. Three months later, visiting scientists were surprised to find one lifeform present in the region: microscopic spiders.

These spiders weren’t on the newborn island because they survived the blast. Rather, they had travelled there in the aftermath of the eruption—by ballooning. Now a well-known phenomenon, ballooning occurs when spiders stream their silk into the air, catching the winds like a sail for loft. Spiders have been found in the middle of the ocean, hitching a ride on the jet stream and on remote islands hundreds of miles from the mainland. Not all spiders balloon to travel extreme distances—some rely on it to flee from predators or cover short lengths without expending much energy.

Mass Production

he production of spider silk in commercial quantities holds the potential of a life-saving ballistic resistant material, which is lighter, thinner, more flexible, and tougher than steel. Other applications of spider silk include use as structural material and for any application in which light weight and high strength are required.[ii]

While scientists have been able to replicate the proteins that are the building blocks of spider silk, two technological barriers have (until now) stymied production. These barriers are the inability to form these proteins into a spider silk fiber with the desired mechanical characteristics, and to do this cost effectively.

Kraig is the world leader in genetically engineered spider silk technologies. We earned that place by applying our proprietary genetic engineering spider silk technology to an organism which is already one of the most efficient commercial producers of silk: The domesticated silkworm.

Kraig’s spider silk technology builds upon the unique advantages of the domesticated silkworm for this application. The silkworm is ideally suited to produce genetically engineered spider silk because it is already an efficient commercial and industrial producer of silk. Forty percent (40%) of the caterpillars’ weight is devoted to the silk glands. The silk glands produce large volumes of protein, called fibroin, which are then spun into a composite protein thread (silk).

Kraig is focused on the creation, production and marketing of high performance and technical fibers such as spider silk. Because spider silks are stronger and tougher than steel, they could be used in a wide variety of military, industrial, and consumer applications ranging from ballistic protection to superior strength and toughness.

The global market demand for technical fibers is growing rapidly and these materials have become essential products for both industrial and consumer applications. By 2012, the annual global market for technical fibers had already reached approximately $133 billion.

Gen 3 fibers are in a relatively early stage of development and will incorporate such elements as antibacterial agents for medical use, and metallic ions for use in industrial processes

Clothing

Now, one Japanese startup, Spiber, is exploring how spider webs could transform the textile industry. The biotech company started by making a spider silk replica in the lab and has since spun out its fabric range to include more sustainable alternatives to wool, cashmere and denim, says Kenji Higashi, head of business development at Spiber.

The company’s trademarked fiber, Brewed Protein, has been used in limited edition collections with brands including Japanese streetwear label Sacai and outdoor apparel specialists The North Face Japan.[iii]

In industries like fashion, these kinds of “structural protein materials” could be an environmentally friendly alternative to petroleum-based or animal-derived fibers, explains Meyer. Fibers made with fossil-fuels (like acrylic and nylon) are incredibly useful, cheap, and durable. But their production is a source of a worsening pollution crisis, as tiny strands and particles make their way into waterways, disrupting delicate ecosystems and even tainting human food supplies.[iv]

7 Types of Spider Silk

Dragline Spider Silk

The most common type of silk is dragline spider silk, which makes up the main scaffolding of a spider’s web. It is made from tough, stretchy protein molecules and stretches to absorb impact without breaking or losing strength. Dragline silks are also used for safety lines when hunting prey in mid-air as they can withstand up to 100 pounds before giving way – making the line good for catching big things like birds.

Flagelliform Spider Silk

This type of silk is used mainly for wrapping prey and building the base of a web. It’s made from sticky protein molecules which are designed to trap insects in webs, making it difficult for them to escape while being devoured by the spider. Flagelliform silks can also be used to create a secure attachment point for the strands of other types of silk, like dragline silks.

Cribellate Spider Silk?

Cribellate spider silk is also known as “spinneret” or “serriculate” silks because it’s made from fine protein filaments that are mainly used by spiders to create a sticky layer on their feet. This type of silk is used for preparing the surface with which they’ll walk when building webs or catching prey from afar. It can also be found in wads at the end of spinnerets, where it’s often mixed up with other types of silks like dragline and flagelliform.

Aciniform Spider Silk

This type of silk is used as a safety line by spiders while catching prey in mid-air, like those pesky birds that steal ripe fruit from your garden! Aciniform silks are made up mainly of protein molecules called “spidroins.” Spiders use these spidroins to create a sticky liquid that can be used as glue, and they’ll spin them into silk thread using their spinnerets. Aciniform silks are the longest type of spider silk – they’re often around 14 feet long and have been known to break under only 20 pounds!

Spidroin Spider Silk

Tough protein molecules called “spidroins” are used by spiders to create a sticky liquid that can be used as glue and spun into silk thread. Spidroin silks have been found in the webs of golden orb-weaving spider species, like Nephila clavipes or Nephilengys malabarensis – they’re often mixed with other types of spider silks like aciniform and dragline.

Spider silk is strong and lightweight. It’s also a good insulator, meaning that it can protect the spider against extreme temperatures and harsh weather conditions. It’s also biodegradable and is spun in a single direction, which makes it difficult to tangle.[v]

Poison or Pharmaceutical?

Australia’s infamously dangerous arachnids have revealed a more benign side, with their deadly venom harboring the potential to block sodium channels involved in pain, epilepsy, and stroke.[vi]

The University of Queensland’s Professor Glenn King is the first to admit his fascination with venom came by chance. A collaborator asked him to analyze a toxin found in the venom of Australia’s deadly funnel-web spider. The work led to clues about the toxin’s function, a paper in Nature Structural and Molecular Biology, and eventually a change in King’s research focus from cancer to venom.

King would eventually discover that funnel-web venom has more than 3,000 components, making it “probably the most complex chemical arsenal in the natural world”.

The research has already yielded an insecticide derived from funnel-web spider venom that is now marketed in the US by Vestaron Corporation, a spin-off company King founded while working at the University of Connecticut.

Funnel-web spider venom contains small proteins or peptides that interact with, and modulate the activity of, ion channels and receptors in mammalian neurons.

That discovery led King and his team to focus on ion channels involved in human disorders such as epilepsy, pain, and stroke. “We know these venoms are full of ion channel modulators, so we thought maybe we could use them as libraries to screen against ion channel drug targets that we know about,” he says.

The approach has had phenomenal success, with King’s laboratory uncovering possible therapies for Dravet syndrome, epilepsy, abdominal pain, and stroke.

Dravet syndrome is a rare and life-threatening form of epilepsy that strikes children in the first year of life. It is caused by a mutation that reduces the amount of Na_V1.1, a key sodium channel in the brain that is critical for regulating brain excitability.

Working in collaboration with Steven Petrou at the Florey Institute of Neuroscience and Mental Health, King’s team found a peptide in funnel-web spider venom that restores normal function of this channel and eliminates seizures.

Funnel-web spider venom has also proven to be the key ingredient in his work on strokes. During a stroke, acid-sensing ion channel 1a is activated and this sets off a death spiral for neurons. King’s team has found a funnel-web spider venom peptide that binds to this channel and stops it from becoming activated during stroke.

With two million neurons dying every minute without treatment, time is of the essence during a stroke.

This is because of lack of blood flow to the organ.

However, as King points out, there are two kinds of stroke. “We have only one drug available for ischemic stroke, but it can make things worse for haemorrhagic stroke, so you can’t give the drug until you get the patient to hospital and image the brain.

“The drug we are developing should be fine for both types of stroke, which means patients could be given the drug straight away and their brain would be protected.”

The discovery’s potential is global, as stroke kills six million people worldwide each year, and leaves five million survivors with a permanent disability. “We are pretty excited about it, but it is also a difficult challenge because we still need to find the best way to get the drug into the brain.”

Meanwhile, his work on gut pain does not require the drug to pass the blood-brain barrier and is closer to clinical trials. “We stumbled across a spider-venom peptide that activated neurons through a different sodium channel that no one thought was involved in pain,” he says. “It turns out this channel is important for the abdominal pain associated with irritable bowel syndrome.”

“We have now found a venom peptide that inhibits this channel and does a great job of stopping the gut pain associated with IBS.”

nves of protein and peptide classes identified in spider venoms. Top panel: large proteins represented by Phospholipase D. Bottom two panels: short spider venom peptides divided into two major classes. The middle panel depicts selected neurotoxic ICK (inhibitor cystine knot) toxins (Versutoxin, Robustoxin and Huwentoxin-I). The lower panel shows representative antimicrobial peptides (Latarcin-II and Oxyopinin). Species names of spiders from which the components were isolated are indicated below the compound names. Secondary structures are indicated by colour (α-helices in blue, β-sheets in red, and turns in purple).[vii]

Brown spider (genus Loxosceles) venoms are mainly composed of protein toxins used for predation and defense. Bites of these spiders most commonly produce a local dermonecrotic lesion with gravitational spread, edema and hemorrhage, which together are defined as cutaneous loxoscelism.

Loxosceles toxins have been identified and functionally characterized, such as hyaluronidases, allergen factor, serpin, TCTP and knottins (ICK peptides). Together, these are candidates to tackle many medical and biological threats, acting, for instance, as antitumoral, insecticides, analgesic, antigens for allergy tests and biochemical reagents for cell studies.[viii]

Lycosin II

Antimicrobial peptides have been accepted as excellent candidates for developing novel antibiotics against drug-resistant bacteria.

Lycosin-II was isolated from the venom of the spider Lycosa singoriensis. It contains 21 amino acid residue lacking cysteine residues and forms a typical linear amphipathic and cationic α-helical conformation. Lycosin-II displays potent bacteriostatic effect on the tested drug-resistant bacterial strains isolated from hospital patients, including multidrug-resistant A. baumannii, which has presented a huge challenge for the infection therapy.

The bacteriostatic effect of lycosin-II might be correlated with its ability to binding to bacterial cell membrane.

A total of 18 strains of bacteria, including 7 Gram-negative bacterial strains from patient ascites, 8 strains of A. baumannii, and 3 strains of Staphylococcus aureus were tested. The results are shown in Table 1. Lycosin-II was able to inhibit the growth of all bacterial strains with MIC values ranging from 3.1 to 25 µM, depending on the type of bacteria tested.

The misuse of antibiotics has caused the continuous emergence of multidrug-resistant A. baumannii isolates. Polymyxins and, possibly, tigecycline are considered to be the last resort of reliable treatments.[ix]

Recently, there has been a growing interest in the discovery of novel chemotherapeutic agents that have fewer side effects and are less likely to develop resistance.

The results of MTT assay (a colorimetric assay for assessing cell metabolic activity) showed that lycosin-II possesses cytotoxicity (IC50=70.79ug/mL) against the human colorectal cancer cell line HCT 116 as these cells were killed 30 min after treatment. Lycosin-II also exhibits a dose-dependent antiproliferative effect. Lactate dehydrogenase leakage assay and scanning electron microscopy revealed that lycosin-II kills tumor cells through membrane disruption.[x]

[i] https://www.smithsonianmag.com/science-nature/fourteen-ways-spiders-use-their-silk-180978354/#:~:text=Spider%20silk%20is%20a%20wonder,cables%20and%20even%20extravagant%20clothing.

[ii] https://www.kraiglabs.com/spider-silk/

[iii] Meet the Japanese spider silk startup behind North Face's $1,300 parka | CNN Business

[iv] Spidersilk: the Future of Sustainable Fashion and… | Supermaker

[v] All About Spider Silk: 7 Types of Silks and How a Spider Makes It – Exotic Pets World

[vi] https://www.nature.com/articles/d42473-018-00315-6

[vii] https://onlinelibrary.wiley.com/doi/full/10.1111/brv.12793

[viii] Gremski LH, Matsubara FH, Polli NLC, Antunes BC, Schluga PHC, da Justa HC, Minozzo JC, Wille ACM, Senff-Ribeiro A, Veiga SS. Prospective Use of Brown Spider Venom Toxins as Therapeutic and Biotechnological Inputs. Front Mol Biosci. 2021 Jun 17;8:706704. doi:

[ix] Toxins Article The Spider Venom Peptide Lycosin-II Has Potent Antimicrobial Activity against Clinically Isolated Bacteria Yongjun Wang 1,2, Ling Wang 3 , Huali Yang 1 , Haoliang Xiao 4 , Athar Farooq 5 , Zhonghua Liu 5 , Min Hu 3,* and Xiaoliu Shi 1,2,*

[x] Afsari, V., Rad, A., Hashemi-Khah, M. et al. Lycosin-II Suppresses the Growth of Tumor Cells and Kills them Through Membrane Disruption and Apoptosis Induction. Int J Pept Res Ther 25, 873–880 (2019).